Skip to main content
Top
Published in: Journal of Hematology & Oncology 1/2022

Open Access 01-12-2022 | Lymphoma | Review

Targeting macrophages in hematological malignancies: recent advances and future directions

Authors: Wei Li, Fang Wang, Rongqun Guo, Zhilei Bian, Yongping Song

Published in: Journal of Hematology & Oncology | Issue 1/2022

Login to get access

Abstract

Emerging evidence indicates that the detection and clearance of cancer cells via phagocytosis induced by innate immune checkpoints play significant roles in tumor-mediated immune escape. The most well-described innate immune checkpoints are the “don’t eat me” signals, including the CD47/signal regulatory protein α axis (SIRPα), PD-1/PD-L1 axis, CD24/SIGLEC-10 axis, and MHC-I/LILRB1 axis. Molecules have been developed to block these pathways and enhance the phagocytic activity against tumors. Several clinical studies have investigated the safety and efficacy of CD47 blockades, either alone or in combination with existing therapy in hematological malignancies, including myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and lymphoma. However, only a minority of patients have significant responses to these treatments alone. Combining CD47 blockades with other treatment modalities are in clinical studies, with early results suggesting a synergistic therapeutic effect. Targeting macrophages with bispecific antibodies are being explored in blood cancer therapy. Furthermore, reprogramming of pro-tumor macrophages to anti-tumor macrophages, and CAR macrophages (CAR-M) demonstrate anti-tumor activities. In this review, we elucidated distinct types of macrophage-targeted strategies in hematological malignancies, from preclinical experiments to clinical trials, and outlined potential therapeutic approaches being developed.
Literature
4.
go back to reference Sharma P, Siddiqui BA, Anandhan S, Yadav SS, Subudhi SK, Gao J, Goswami S, Allison JP. The next decade of immune checkpoint therapy. Cancer Discov. 2021;11(4):838–57.PubMedCrossRef Sharma P, Siddiqui BA, Anandhan S, Yadav SS, Subudhi SK, Gao J, Goswami S, Allison JP. The next decade of immune checkpoint therapy. Cancer Discov. 2021;11(4):838–57.PubMedCrossRef
5.
go back to reference Wu M, Huang Q, Xie Y, Wu X, Ma H, Zhang Y, Xia Y. Improvement of the anticancer efficacy of PD-1/PD-L1 blockade via combination therapy and PD-L1 regulation. J Hematol Oncol. 2022;15(1):24.PubMedPubMedCentralCrossRef Wu M, Huang Q, Xie Y, Wu X, Ma H, Zhang Y, Xia Y. Improvement of the anticancer efficacy of PD-1/PD-L1 blockade via combination therapy and PD-L1 regulation. J Hematol Oncol. 2022;15(1):24.PubMedPubMedCentralCrossRef
7.
go back to reference Chen Y, Wang Y, Luo H, Meng X, Zhu W, Wang D, Zeng H, Zhang H. The frequency and inter-relationship of PD-L1 expression and tumour mutational burden across multiple types of advanced solid tumours in China. Exp Hematol Oncol. 2020;9(1):17.PubMedPubMedCentralCrossRef Chen Y, Wang Y, Luo H, Meng X, Zhu W, Wang D, Zeng H, Zhang H. The frequency and inter-relationship of PD-L1 expression and tumour mutational burden across multiple types of advanced solid tumours in China. Exp Hematol Oncol. 2020;9(1):17.PubMedPubMedCentralCrossRef
8.
go back to reference Kubli SP, Berger T, Araujo DV, Siu LL, Mak TW. Beyond immune checkpoint blockade: emerging immunological strategies. Nat Rev Drug Discov. 2021;20(12):899–919.PubMedCrossRef Kubli SP, Berger T, Araujo DV, Siu LL, Mak TW. Beyond immune checkpoint blockade: emerging immunological strategies. Nat Rev Drug Discov. 2021;20(12):899–919.PubMedCrossRef
9.
go back to reference Sun J-Y, Zhang D, Wu S, Xu M, Zhou X, Lu X-J, Ji J. Resistance to PD-1/PD-L1 blockade cancer immunotherapy: mechanisms, predictive factors, and future perspectives. Biomark Res. 2020;8(1):35.PubMedPubMedCentralCrossRef Sun J-Y, Zhang D, Wu S, Xu M, Zhou X, Lu X-J, Ji J. Resistance to PD-1/PD-L1 blockade cancer immunotherapy: mechanisms, predictive factors, and future perspectives. Biomark Res. 2020;8(1):35.PubMedPubMedCentralCrossRef
10.
go back to reference Liu F, Qin L, Liao Z, Song J, Yuan C, Liu Y, Wang Y, Xu H, Zhang Q, Pei Y, et al. Microenvironment characterization and multi-omics signatures related to prognosis and immunotherapy response of hepatocellular carcinoma. Exp Hematol Oncol. 2020;9(1):10.PubMedPubMedCentralCrossRef Liu F, Qin L, Liao Z, Song J, Yuan C, Liu Y, Wang Y, Xu H, Zhang Q, Pei Y, et al. Microenvironment characterization and multi-omics signatures related to prognosis and immunotherapy response of hepatocellular carcinoma. Exp Hematol Oncol. 2020;9(1):10.PubMedPubMedCentralCrossRef
11.
go back to reference Kim TK, Vandsemb EN, Herbst RS, Chen L. Adaptive immune resistance at the tumour site: mechanisms and therapeutic opportunities. Nat Rev Drug Discov 2022. Kim TK, Vandsemb EN, Herbst RS, Chen L. Adaptive immune resistance at the tumour site: mechanisms and therapeutic opportunities. Nat Rev Drug Discov 2022.
12.
14.
go back to reference Tan J, Yu Z, Huang J, Chen Y, Huang S, Yao D, Xu L, Lu Y, Chen S, Li Y. Increased PD-1+Tim-3+ exhausted T cells in bone marrow may influence the clinical outcome of patients with AML. Biomark Res. 2020;8(1):6.PubMedPubMedCentralCrossRef Tan J, Yu Z, Huang J, Chen Y, Huang S, Yao D, Xu L, Lu Y, Chen S, Li Y. Increased PD-1+Tim-3+ exhausted T cells in bone marrow may influence the clinical outcome of patients with AML. Biomark Res. 2020;8(1):6.PubMedPubMedCentralCrossRef
16.
go back to reference Zhu S, Zhang T, Zheng L, Liu H, Song W, Liu D, Li Z. Pan C-x: Combination strategies to maximize the benefits of cancer immunotherapy. J Hematol Oncol. 2021;14(1):156.PubMedPubMedCentralCrossRef Zhu S, Zhang T, Zheng L, Liu H, Song W, Liu D, Li Z. Pan C-x: Combination strategies to maximize the benefits of cancer immunotherapy. J Hematol Oncol. 2021;14(1):156.PubMedPubMedCentralCrossRef
18.
go back to reference Holmström MO, Cordua S, Skov V, Kjær L, Pallisgaard N, Ellervik C, Hasselbalch HC, Andersen MH. Evidence of immune elimination, immuno-editing and immune escape in patients with hematological cancer. Cancer Immunol Immunother. 2020;69(2):315–24.PubMedCrossRef Holmström MO, Cordua S, Skov V, Kjær L, Pallisgaard N, Ellervik C, Hasselbalch HC, Andersen MH. Evidence of immune elimination, immuno-editing and immune escape in patients with hematological cancer. Cancer Immunol Immunother. 2020;69(2):315–24.PubMedCrossRef
19.
go back to reference Swamydas M, Murphy EV, Ignatz-Hoover JJ, Malek E, Driscoll JJ. Deciphering mechanisms of immune escape to inform immunotherapeutic strategies in multiple myeloma. J Hematol Oncol. 2022;15(1):17.PubMedPubMedCentralCrossRef Swamydas M, Murphy EV, Ignatz-Hoover JJ, Malek E, Driscoll JJ. Deciphering mechanisms of immune escape to inform immunotherapeutic strategies in multiple myeloma. J Hematol Oncol. 2022;15(1):17.PubMedPubMedCentralCrossRef
20.
go back to reference Guillerey C, Huntington ND, Smyth MJ. Targeting natural killer cells in cancer immunotherapy. Nat Immunol. 2016;17(9):1025–36.PubMedCrossRef Guillerey C, Huntington ND, Smyth MJ. Targeting natural killer cells in cancer immunotherapy. Nat Immunol. 2016;17(9):1025–36.PubMedCrossRef
21.
go back to reference Christopher MJ, Petti AA, Rettig MP, Miller CA, Chendamarai E, Duncavage EJ, Klco JM, Helton NM, O’Laughlin M, Fronick CC, et al. Immune escape of relapsed AML cells after allogeneic transplantation. N Engl J Med. 2018;379(24):2330–41.PubMedPubMedCentralCrossRef Christopher MJ, Petti AA, Rettig MP, Miller CA, Chendamarai E, Duncavage EJ, Klco JM, Helton NM, O’Laughlin M, Fronick CC, et al. Immune escape of relapsed AML cells after allogeneic transplantation. N Engl J Med. 2018;379(24):2330–41.PubMedPubMedCentralCrossRef
22.
go back to reference Feng M, Jiang W, Kim BYS, Zhang CC, Fu YX, Weissman IL. Phagocytosis checkpoints as new targets for cancer immunotherapy. Nat Rev Cancer. 2019;19(10):568–86.PubMedPubMedCentralCrossRef Feng M, Jiang W, Kim BYS, Zhang CC, Fu YX, Weissman IL. Phagocytosis checkpoints as new targets for cancer immunotherapy. Nat Rev Cancer. 2019;19(10):568–86.PubMedPubMedCentralCrossRef
24.
25.
go back to reference Jaillon S, Ponzetta A, Di Mitri D, Santoni A, Bonecchi R, Mantovani A. Neutrophil diversity and plasticity in tumour progression and therapy. Nat Rev Cancer. 2020;20(9):485–503.PubMedCrossRef Jaillon S, Ponzetta A, Di Mitri D, Santoni A, Bonecchi R, Mantovani A. Neutrophil diversity and plasticity in tumour progression and therapy. Nat Rev Cancer. 2020;20(9):485–503.PubMedCrossRef
26.
27.
go back to reference Wu Q, You L, Nepovimova E, Heger Z, Wu W, Kuca K, Adam V. Hypoxia-inducible factors: master regulators of hypoxic tumor immune escape. J Hematol Oncol. 2022;15(1):77.PubMedPubMedCentralCrossRef Wu Q, You L, Nepovimova E, Heger Z, Wu W, Kuca K, Adam V. Hypoxia-inducible factors: master regulators of hypoxic tumor immune escape. J Hematol Oncol. 2022;15(1):77.PubMedPubMedCentralCrossRef
28.
go back to reference Xiao N, Zhu X, Li K, Chen Y, Liu X, Xu B, Lei M, Xu J, Sun H-C. Blocking siglec-10hi tumor-associated macrophages improves anti-tumor immunity and enhances immunotherapy for hepatocellular carcinoma. Exp Hematol Oncol. 2021;10(1):1–14.CrossRef Xiao N, Zhu X, Li K, Chen Y, Liu X, Xu B, Lei M, Xu J, Sun H-C. Blocking siglec-10hi tumor-associated macrophages improves anti-tumor immunity and enhances immunotherapy for hepatocellular carcinoma. Exp Hematol Oncol. 2021;10(1):1–14.CrossRef
29.
go back to reference Pittet MJ, Michielin O, Migliorini D. Clinical relevance of tumour-associated macrophages. Nat Rev Clin Oncol. 2022;19(6):402–21.PubMedCrossRef Pittet MJ, Michielin O, Migliorini D. Clinical relevance of tumour-associated macrophages. Nat Rev Clin Oncol. 2022;19(6):402–21.PubMedCrossRef
31.
go back to reference Oldenborg PA, Gresham HD, Lindberg FP. CD47-signal regulatory protein alpha (SIRPalpha) regulates Fcgamma and complement receptor-mediated phagocytosis. J Exp Med. 2001;193(7):855–62.PubMedPubMedCentralCrossRef Oldenborg PA, Gresham HD, Lindberg FP. CD47-signal regulatory protein alpha (SIRPalpha) regulates Fcgamma and complement receptor-mediated phagocytosis. J Exp Med. 2001;193(7):855–62.PubMedPubMedCentralCrossRef
32.
go back to reference Willingham SB, Volkmer JP, Gentles AJ, Sahoo D, Dalerba P, Mitra SS, Wang J, Contreras-Trujillo H, Martin R, Cohen JD, et al. The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors. Proc Natl Acad Sci USA. 2012;109(17):6662–7.PubMedPubMedCentralCrossRef Willingham SB, Volkmer JP, Gentles AJ, Sahoo D, Dalerba P, Mitra SS, Wang J, Contreras-Trujillo H, Martin R, Cohen JD, et al. The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors. Proc Natl Acad Sci USA. 2012;109(17):6662–7.PubMedPubMedCentralCrossRef
33.
34.
go back to reference Majeti R, Chao MP, Alizadeh AA, Pang WW, Jaiswal S, Gibbs KD Jr, van Rooijen N, Weissman IL. CD47 is an adverse prognostic factor and therapeutic antibody target on human acute myeloid leukemia stem cells. Cell. 2009;138(2):286–99.PubMedPubMedCentralCrossRef Majeti R, Chao MP, Alizadeh AA, Pang WW, Jaiswal S, Gibbs KD Jr, van Rooijen N, Weissman IL. CD47 is an adverse prognostic factor and therapeutic antibody target on human acute myeloid leukemia stem cells. Cell. 2009;138(2):286–99.PubMedPubMedCentralCrossRef
35.
go back to reference Chao MP, Alizadeh AA, Tang C, Myklebust JH, Varghese B, Gill S, Jan M, Cha AC, Chan CK, Tan BT, et al. Anti-CD47 antibody synergizes with rituximab to promote phagocytosis and eradicate non-Hodgkin lymphoma. Cell. 2010;142(5):699–713.PubMedPubMedCentralCrossRef Chao MP, Alizadeh AA, Tang C, Myklebust JH, Varghese B, Gill S, Jan M, Cha AC, Chan CK, Tan BT, et al. Anti-CD47 antibody synergizes with rituximab to promote phagocytosis and eradicate non-Hodgkin lymphoma. Cell. 2010;142(5):699–713.PubMedPubMedCentralCrossRef
36.
go back to reference Uger R, Johnson L. Blockade of the CD47-SIRPα axis: a promising approach for cancer immunotherapy. Expert Opin Biol Ther. 2020;20(1):5–8.PubMedCrossRef Uger R, Johnson L. Blockade of the CD47-SIRPα axis: a promising approach for cancer immunotherapy. Expert Opin Biol Ther. 2020;20(1):5–8.PubMedCrossRef
37.
go back to reference Theruvath J, Menard M, Smith BAH, Linde MH, Coles GL, Dalton GN, Wu W, Kiru L, Delaidelli A, Sotillo E, et al. Anti-GD2 synergizes with CD47 blockade to mediate tumor eradication. Nat Med. 2022;28(2):333–44.PubMedPubMedCentralCrossRef Theruvath J, Menard M, Smith BAH, Linde MH, Coles GL, Dalton GN, Wu W, Kiru L, Delaidelli A, Sotillo E, et al. Anti-GD2 synergizes with CD47 blockade to mediate tumor eradication. Nat Med. 2022;28(2):333–44.PubMedPubMedCentralCrossRef
38.
go back to reference Upton R, Banuelos A, Feng D, Biswas T, Kao K, McKenna K, Willingham S, Ho PY, Rosental B, Tal MC, et al. Combining CD47 blockade with trastuzumab eliminates HER2-positive breast cancer cells and overcomes trastuzumab tolerance. Proc Natl Acad Sci. 2021;118(29): e2026849118.PubMedPubMedCentralCrossRef Upton R, Banuelos A, Feng D, Biswas T, Kao K, McKenna K, Willingham S, Ho PY, Rosental B, Tal MC, et al. Combining CD47 blockade with trastuzumab eliminates HER2-positive breast cancer cells and overcomes trastuzumab tolerance. Proc Natl Acad Sci. 2021;118(29): e2026849118.PubMedPubMedCentralCrossRef
39.
go back to reference Mehta A, Harb W, Xu C, Meng Y, Lee L, Yuan V, Wang Z, Song P, Shen JH, Gopal AK. Lemzoparlimab, a differentiated anti-cd47 antibody in combination with rituximab in relapsed and refractory non-Hodgkin’s lymphoma: initial clinical results. Blood. 2021;138:3542.CrossRef Mehta A, Harb W, Xu C, Meng Y, Lee L, Yuan V, Wang Z, Song P, Shen JH, Gopal AK. Lemzoparlimab, a differentiated anti-cd47 antibody in combination with rituximab in relapsed and refractory non-Hodgkin’s lymphoma: initial clinical results. Blood. 2021;138:3542.CrossRef
40.
go back to reference Cao X, Wang Y, Zhang W, Zhong X, Gunes EG, Dang J, Wang J, Epstein AL, Querfeld C, Sun Z et al. Targeting macrophages for enhancing CD47 blockade-elicited lymphoma clearance and overcoming tumor-induced suppression. Blood 2022. Cao X, Wang Y, Zhang W, Zhong X, Gunes EG, Dang J, Wang J, Epstein AL, Querfeld C, Sun Z et al. Targeting macrophages for enhancing CD47 blockade-elicited lymphoma clearance and overcoming tumor-induced suppression. Blood 2022.
41.
go back to reference Garcia-Manero G, Daver NG, Xu J, Chao M, Chung T, Tan A, Wang V, Wei A, Vyas P, Sallman DA. Magrolimab + azacitidine versus azacitidine + placebo in untreated higher risk (HR) myelodysplastic syndrome (MDS): The phase 3, randomized, ENHANCE study. J Clin Oncol 2021;39(15_suppl):TPS7055–TPS7055. Garcia-Manero G, Daver NG, Xu J, Chao M, Chung T, Tan A, Wang V, Wei A, Vyas P, Sallman DA. Magrolimab + azacitidine versus azacitidine + placebo in untreated higher risk (HR) myelodysplastic syndrome (MDS): The phase 3, randomized, ENHANCE study. J Clin Oncol 2021;39(15_suppl):TPS7055–TPS7055.
42.
go back to reference Advani R, Flinn I, Popplewell L, Forero A, Bartlett NL, Ghosh N, Kline J, Roschewski M, LaCasce A, Collins GP. CD47 blockade by Hu5F9-G4 and rituximab in non-Hodgkin’s lymphoma. N Engl J Med. 2018;379(18):1711–21.PubMedPubMedCentralCrossRef Advani R, Flinn I, Popplewell L, Forero A, Bartlett NL, Ghosh N, Kline J, Roschewski M, LaCasce A, Collins GP. CD47 blockade by Hu5F9-G4 and rituximab in non-Hodgkin’s lymphoma. N Engl J Med. 2018;379(18):1711–21.PubMedPubMedCentralCrossRef
43.
go back to reference Gordon SR, Maute RL, Dulken BW, Hutter G, George BM, McCracken MN, Gupta R, Tsai JM, Sinha R, Corey D. PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity. Nature. 2017;545(7655):495–9.PubMedPubMedCentralCrossRef Gordon SR, Maute RL, Dulken BW, Hutter G, George BM, McCracken MN, Gupta R, Tsai JM, Sinha R, Corey D. PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity. Nature. 2017;545(7655):495–9.PubMedPubMedCentralCrossRef
44.
go back to reference Barkal AA, Weiskopf K, Kao KS, Gordon SR, Rosental B, Yiu YY, George BM, Markovic M, Ring NG, Tsai JM. Engagement of MHC class I by the inhibitory receptor LILRB1 suppresses macrophages and is a target of cancer immunotherapy. Nat Immunol. 2018;19(1):76–84.PubMedCrossRef Barkal AA, Weiskopf K, Kao KS, Gordon SR, Rosental B, Yiu YY, George BM, Markovic M, Ring NG, Tsai JM. Engagement of MHC class I by the inhibitory receptor LILRB1 suppresses macrophages and is a target of cancer immunotherapy. Nat Immunol. 2018;19(1):76–84.PubMedCrossRef
45.
go back to reference Zhao J, Zhong S, Niu X, Jiang J, Zhang R, Li Q. The MHC class I-LILRB1 signalling axis as a promising target in cancer therapy. Scand J Immunol. 2019;90(5): e12804.PubMedCrossRef Zhao J, Zhong S, Niu X, Jiang J, Zhang R, Li Q. The MHC class I-LILRB1 signalling axis as a promising target in cancer therapy. Scand J Immunol. 2019;90(5): e12804.PubMedCrossRef
46.
go back to reference Chen H-M, van der Touw W, Wang YS, Kang K, Mai S, Zhang J, Alsina-Beauchamp D, Duty JA, Mungamuri SK, Zhang B. Blocking immunoinhibitory receptor LILRB2 reprograms tumor-associated myeloid cells and promotes antitumor immunity. J Clin Investig. 2018;128(12):5647–62.PubMedPubMedCentralCrossRef Chen H-M, van der Touw W, Wang YS, Kang K, Mai S, Zhang J, Alsina-Beauchamp D, Duty JA, Mungamuri SK, Zhang B. Blocking immunoinhibitory receptor LILRB2 reprograms tumor-associated myeloid cells and promotes antitumor immunity. J Clin Investig. 2018;128(12):5647–62.PubMedPubMedCentralCrossRef
47.
go back to reference Barkal AA, Brewer RE, Markovic M, Kowarsky M, Barkal SA, Zaro BW, Krishnan V, Hatakeyama J, Dorigo O, Barkal LJ. CD24 signalling through macrophage Siglec-10 is a target for cancer immunotherapy. Nature. 2019;572(7769):392–6.PubMedPubMedCentralCrossRef Barkal AA, Brewer RE, Markovic M, Kowarsky M, Barkal SA, Zaro BW, Krishnan V, Hatakeyama J, Dorigo O, Barkal LJ. CD24 signalling through macrophage Siglec-10 is a target for cancer immunotherapy. Nature. 2019;572(7769):392–6.PubMedPubMedCentralCrossRef
48.
go back to reference Rojo R, Raper A, Ozdemir DD, Lefevre L, Grabert K, Wollscheid-Lengeling E, Bradford B, Caruso M, Gazova I, Sánchez A. Deletion of a Csf1r enhancer selectively impacts CSF1R expression and development of tissue macrophage populations. Nat Commun. 2019;10(1):1–17.CrossRef Rojo R, Raper A, Ozdemir DD, Lefevre L, Grabert K, Wollscheid-Lengeling E, Bradford B, Caruso M, Gazova I, Sánchez A. Deletion of a Csf1r enhancer selectively impacts CSF1R expression and development of tissue macrophage populations. Nat Commun. 2019;10(1):1–17.CrossRef
49.
go back to reference Zhu Y, Knolhoff BL, Meyer MA, Nywening TM, West BL, Luo J, Wang-Gillam A, Goedegebuure SP, Linehan DC, DeNardo DG. CSF1/CSF1R blockade reprograms tumor-infiltrating macrophages and improves response to T-cell checkpoint immunotherapy in pancreatic cancer models. Can Res. 2014;74(18):5057–69.CrossRef Zhu Y, Knolhoff BL, Meyer MA, Nywening TM, West BL, Luo J, Wang-Gillam A, Goedegebuure SP, Linehan DC, DeNardo DG. CSF1/CSF1R blockade reprograms tumor-infiltrating macrophages and improves response to T-cell checkpoint immunotherapy in pancreatic cancer models. Can Res. 2014;74(18):5057–69.CrossRef
50.
go back to reference Zhang Z, Luo F, Cao J, Lu F, Zhang Y, Ma Y, Zeng K, Zhang L, Zhao H. Anticancer bispecific antibody R&D advances: a study focusing on research trend worldwide and in China. J Hematol Oncol. 2021;14(1):124.PubMedPubMedCentralCrossRef Zhang Z, Luo F, Cao J, Lu F, Zhang Y, Ma Y, Zeng K, Zhang L, Zhao H. Anticancer bispecific antibody R&D advances: a study focusing on research trend worldwide and in China. J Hematol Oncol. 2021;14(1):124.PubMedPubMedCentralCrossRef
51.
53.
go back to reference Piccione EC, Juarez S, Liu J, Tseng S, Ryan CE, Narayanan C, Wang L, Weiskopf K, Majeti R. A bispecific antibody targeting CD47 and CD20 selectively binds and eliminates dual antigen expressing lymphoma cells. In: MAbs: 2015: Taylor & Francis; 2015;946–956. Piccione EC, Juarez S, Liu J, Tseng S, Ryan CE, Narayanan C, Wang L, Weiskopf K, Majeti R. A bispecific antibody targeting CD47 and CD20 selectively binds and eliminates dual antigen expressing lymphoma cells. In: MAbs: 2015: Taylor & Francis; 2015;946–956.
54.
go back to reference van Bommel PE, He Y, Schepel I, Hendriks MA, Wiersma VR, van Ginkel RJ, van Meerten T, Ammatuna E, Huls G, Samplonius DF. CD20-selective inhibition of CD47-SIRPα “don’t eat me” signaling with a bispecific antibody-derivative enhances the anticancer activity of daratumumab, alemtuzumab and obinutuzumab. Oncoimmunology. 2018;7(2): e1386361.PubMedCrossRef van Bommel PE, He Y, Schepel I, Hendriks MA, Wiersma VR, van Ginkel RJ, van Meerten T, Ammatuna E, Huls G, Samplonius DF. CD20-selective inhibition of CD47-SIRPα “don’t eat me” signaling with a bispecific antibody-derivative enhances the anticancer activity of daratumumab, alemtuzumab and obinutuzumab. Oncoimmunology. 2018;7(2): e1386361.PubMedCrossRef
55.
go back to reference Ma L, Zhu M, Gai J, Li G, Chang Q, Qiao P, Cao L, Chen W, Zhang S, Wan Y. Preclinical development of a novel CD47 nanobody with less toxicity and enhanced anti-cancer therapeutic potential. J Nanobiotechnol. 2020;18(1):1–15.CrossRef Ma L, Zhu M, Gai J, Li G, Chang Q, Qiao P, Cao L, Chen W, Zhang S, Wan Y. Preclinical development of a novel CD47 nanobody with less toxicity and enhanced anti-cancer therapeutic potential. J Nanobiotechnol. 2020;18(1):1–15.CrossRef
56.
go back to reference Johnson Z, Papaioannou A, Bernard L, Cosimo E, Daubeuf B, Richard F, Chauchet X, Moine V, Broyer L, Shang L. Bispecific antibody targeting of CD47/CD19 to promote enhanced phagocytosis of patient B lymphoma cells. American Society of Clinical Oncology; 2015.CrossRef Johnson Z, Papaioannou A, Bernard L, Cosimo E, Daubeuf B, Richard F, Chauchet X, Moine V, Broyer L, Shang L. Bispecific antibody targeting of CD47/CD19 to promote enhanced phagocytosis of patient B lymphoma cells. American Society of Clinical Oncology; 2015.CrossRef
57.
go back to reference Buatois V, Johnson Z, Salgado-Pires S, Papaioannou A, Hatterer E, Chauchet X, Richard F, Barba L, Daubeuf B, Cons L. Preclinical development of a bispecific antibody that safely and effectively targets CD19 and CD47 for the treatment of B-cell lymphoma and leukemia. Mol Cancer Ther. 2018;17(8):1739–51.PubMedPubMedCentralCrossRef Buatois V, Johnson Z, Salgado-Pires S, Papaioannou A, Hatterer E, Chauchet X, Richard F, Barba L, Daubeuf B, Cons L. Preclinical development of a bispecific antibody that safely and effectively targets CD19 and CD47 for the treatment of B-cell lymphoma and leukemia. Mol Cancer Ther. 2018;17(8):1739–51.PubMedPubMedCentralCrossRef
58.
go back to reference Ribeiro ML, Normant E, Garau DR, Miskin HP, Sportelli P, Weiss MS, Bosch F, Roué G. PS1310 the novel bispecific CD47-CD19 antibody TG-1801 potentiates the activity of UBLITUXIMAB-UMBRALISIB (U2) drug combination in preclinical models of B-NHL. HemaSphere. 2019;3(S1):598.CrossRef Ribeiro ML, Normant E, Garau DR, Miskin HP, Sportelli P, Weiss MS, Bosch F, Roué G. PS1310 the novel bispecific CD47-CD19 antibody TG-1801 potentiates the activity of UBLITUXIMAB-UMBRALISIB (U2) drug combination in preclinical models of B-NHL. HemaSphere. 2019;3(S1):598.CrossRef
59.
go back to reference Hatterer E, Barba L, Noraz N, Daubeuf B, Aubry-Lachainaye J-P, von der Weid B, Richard F, Kosco-Vilbois M, Ferlin W, Shang L. Co-engaging CD47 and CD19 with a bispecific antibody abrogates B-cell receptor/CD19 association leading to impaired B-cell proliferation. In: MAbs: 2019: Taylor & Francis; 2019: 322–334. Hatterer E, Barba L, Noraz N, Daubeuf B, Aubry-Lachainaye J-P, von der Weid B, Richard F, Kosco-Vilbois M, Ferlin W, Shang L. Co-engaging CD47 and CD19 with a bispecific antibody abrogates B-cell receptor/CD19 association leading to impaired B-cell proliferation. In: MAbs: 2019: Taylor & Francis; 2019: 322–334.
60.
go back to reference Boyd-Kirkup J, Thakkar D, Brauer P, Zhou J, Chng W-J, Ingram PJ. HMBD004, a novel anti-CD47xCD33 bispecific antibody displays potent anti-tumor effects in pre-clinical models of AML. Blood. 2017;130:1378. Boyd-Kirkup J, Thakkar D, Brauer P, Zhou J, Chng W-J, Ingram PJ. HMBD004, a novel anti-CD47xCD33 bispecific antibody displays potent anti-tumor effects in pre-clinical models of AML. Blood. 2017;130:1378.
61.
go back to reference Wang Y, Ni H, Zhou S, He K, Gao Y, Wu W, Wu M, Wu Z, Qiu X, Zhou Y. Tumor-selective blockade of CD47 signaling with a CD47/PD-L1 bispecific antibody for enhanced anti-tumor activity and limited toxicity. Cancer Immunol Immunother. 2021;70(2):365–76.PubMedCrossRef Wang Y, Ni H, Zhou S, He K, Gao Y, Wu W, Wu M, Wu Z, Qiu X, Zhou Y. Tumor-selective blockade of CD47 signaling with a CD47/PD-L1 bispecific antibody for enhanced anti-tumor activity and limited toxicity. Cancer Immunol Immunother. 2021;70(2):365–76.PubMedCrossRef
62.
go back to reference Roohullah A, Ganju V, Zhang F, Zhang L, Yu T, Wilkinson K, Cooper A, de Souza P. First-in-human phase 1 dose escalation study of HX009, a novel recombinant humanized anti-PD-1 and CD47 bispecific antibody, in patients with advanced malignancies. In.: Wolters Kluwer Health; 2021. Roohullah A, Ganju V, Zhang F, Zhang L, Yu T, Wilkinson K, Cooper A, de Souza P. First-in-human phase 1 dose escalation study of HX009, a novel recombinant humanized anti-PD-1 and CD47 bispecific antibody, in patients with advanced malignancies. In.: Wolters Kluwer Health; 2021.
63.
go back to reference Li X, Liu R, Su X, Pan Y, Han X, Shao C, Shi Y. Harnessing tumor-associated macrophages as aids for cancer immunotherapy. Mol Cancer. 2019;18(1):1–16.PubMedPubMedCentralCrossRef Li X, Liu R, Su X, Pan Y, Han X, Shao C, Shi Y. Harnessing tumor-associated macrophages as aids for cancer immunotherapy. Mol Cancer. 2019;18(1):1–16.PubMedPubMedCentralCrossRef
65.
go back to reference Zhang L, Tian L, Dai X, Yu H, Wang J, Lei A, Zhu M, Xu J, Zhao W, Zhu Y. Pluripotent stem cell-derived CAR-macrophage cells with antigen-dependent anti-cancer cell functions. J Hematol Oncol. 2020;13(1):1–5.CrossRef Zhang L, Tian L, Dai X, Yu H, Wang J, Lei A, Zhu M, Xu J, Zhao W, Zhu Y. Pluripotent stem cell-derived CAR-macrophage cells with antigen-dependent anti-cancer cell functions. J Hematol Oncol. 2020;13(1):1–5.CrossRef
66.
go back to reference Klichinsky M, Ruella M, Shestova O, Lu XM, Best A, Zeeman M, Schmierer M, Gabrusiewicz K, Anderson NR, Petty NE. Human chimeric antigen receptor macrophages for cancer immunotherapy. Nat Biotechnol. 2020;38(8):947–53.PubMedPubMedCentralCrossRef Klichinsky M, Ruella M, Shestova O, Lu XM, Best A, Zeeman M, Schmierer M, Gabrusiewicz K, Anderson NR, Petty NE. Human chimeric antigen receptor macrophages for cancer immunotherapy. Nat Biotechnol. 2020;38(8):947–53.PubMedPubMedCentralCrossRef
67.
go back to reference Niu Z, Chen G, Chang W, Sun P, Luo Z, Zhang H, Zhi L, Guo C, Chen H, Yin M. Chimeric antigen receptor-modified macrophages trigger systemic anti-tumour immunity. J Pathol. 2021;253(3):247–57.PubMedCrossRef Niu Z, Chen G, Chang W, Sun P, Luo Z, Zhang H, Zhi L, Guo C, Chen H, Yin M. Chimeric antigen receptor-modified macrophages trigger systemic anti-tumour immunity. J Pathol. 2021;253(3):247–57.PubMedCrossRef
68.
69.
go back to reference Knapp W, Rieber P, Dörken B, Schmidt R, Stein H, Vd Borne AK. Towards a better definition of human leucocyte surface molecules. Immunol Today. 1989;10(8):253–8.PubMedCrossRef Knapp W, Rieber P, Dörken B, Schmidt R, Stein H, Vd Borne AK. Towards a better definition of human leucocyte surface molecules. Immunol Today. 1989;10(8):253–8.PubMedCrossRef
71.
go back to reference Theurl I, Hilgendorf I, Nairz M, Tymoszuk P, Haschka D, Asshoff M, He S, Gerhardt L, Holderried TA, Seifert M. On-demand erythrocyte disposal and iron recycling requires transient macrophages in the liver. Nat Med. 2016;22(8):945–51.PubMedPubMedCentralCrossRef Theurl I, Hilgendorf I, Nairz M, Tymoszuk P, Haschka D, Asshoff M, He S, Gerhardt L, Holderried TA, Seifert M. On-demand erythrocyte disposal and iron recycling requires transient macrophages in the liver. Nat Med. 2016;22(8):945–51.PubMedPubMedCentralCrossRef
72.
go back to reference Li W, Wang Y, Zhao H, Zhang H, Xu Y, Wang S, Guo X, Huang Y, Zhang S, Han Y. Identification and transcriptome analysis of erythroblastic island macrophages. Blood. 2019;134(5):480–91.PubMedPubMedCentralCrossRef Li W, Wang Y, Zhao H, Zhang H, Xu Y, Wang S, Guo X, Huang Y, Zhang S, Han Y. Identification and transcriptome analysis of erythroblastic island macrophages. Blood. 2019;134(5):480–91.PubMedPubMedCentralCrossRef
74.
go back to reference Li W, Guo R, Song Y, Jiang Z. Erythroblastic Island macrophages shape normal erythropoiesis and drive associated disorders in erythroid hematopoietic diseases. Front Cell Dev Biol. 1858;2021:8. Li W, Guo R, Song Y, Jiang Z. Erythroblastic Island macrophages shape normal erythropoiesis and drive associated disorders in erythroid hematopoietic diseases. Front Cell Dev Biol. 1858;2021:8.
75.
go back to reference Oldenborg P-A, Zheleznyak A, Fang Y-F, Lagenaur CF, Gresham HD, Lindberg FP. Role of CD47 as a marker of self on red blood cells. Science. 2000;288(5473):2051–4.PubMedCrossRef Oldenborg P-A, Zheleznyak A, Fang Y-F, Lagenaur CF, Gresham HD, Lindberg FP. Role of CD47 as a marker of self on red blood cells. Science. 2000;288(5473):2051–4.PubMedCrossRef
77.
go back to reference Wang H, VerHalen J, Madariaga ML, Xiang S, Wang S, Lan P, Oldenborg P-A, Sykes M, Yang Y-G. Attenuation of phagocytosis of xenogeneic cells by manipulating CD47. Blood. 2007;109(2):836–42.PubMedPubMedCentralCrossRef Wang H, VerHalen J, Madariaga ML, Xiang S, Wang S, Lan P, Oldenborg P-A, Sykes M, Yang Y-G. Attenuation of phagocytosis of xenogeneic cells by manipulating CD47. Blood. 2007;109(2):836–42.PubMedPubMedCentralCrossRef
78.
go back to reference Yamao T, Noguchi T, Takeuchi O, Nishiyama U, Morita H, Hagiwara T, Akahori H, Kato T, Inagaki K, Okazawa H. Negative regulation of platelet clearance and of the macrophage phagocytic response by the transmembrane glycoprotein SHPS-1. J Biol Chem. 2002;277(42):39833–9.PubMedCrossRef Yamao T, Noguchi T, Takeuchi O, Nishiyama U, Morita H, Hagiwara T, Akahori H, Kato T, Inagaki K, Okazawa H. Negative regulation of platelet clearance and of the macrophage phagocytic response by the transmembrane glycoprotein SHPS-1. J Biol Chem. 2002;277(42):39833–9.PubMedCrossRef
79.
go back to reference Olsson M, Bruhns P, Frazier WA, Ravetch JV, Oldenborg P-A. Platelet homeostasis is regulated by platelet expression of CD47 under normal conditions and in passive immune thrombocytopenia. Blood. 2005;105(9):3577–82.PubMedPubMedCentralCrossRef Olsson M, Bruhns P, Frazier WA, Ravetch JV, Oldenborg P-A. Platelet homeostasis is regulated by platelet expression of CD47 under normal conditions and in passive immune thrombocytopenia. Blood. 2005;105(9):3577–82.PubMedPubMedCentralCrossRef
80.
go back to reference Blazar BR, Lindberg FP, Ingulli E, Panoskaltsis-Mortari A, Oldenborg P-A, Iizuka K, Yokoyama WM, Taylor PA. CD47 (integrin-associated protein) engagement of dendritic cell and macrophage counterreceptors is required to prevent the clearance of donor lymphohematopoietic cells. J Exp Med. 2001;194(4):541–50.PubMedPubMedCentralCrossRef Blazar BR, Lindberg FP, Ingulli E, Panoskaltsis-Mortari A, Oldenborg P-A, Iizuka K, Yokoyama WM, Taylor PA. CD47 (integrin-associated protein) engagement of dendritic cell and macrophage counterreceptors is required to prevent the clearance of donor lymphohematopoietic cells. J Exp Med. 2001;194(4):541–50.PubMedPubMedCentralCrossRef
81.
go back to reference Jaiswal S, Jamieson CH, Pang WW, Park CY, Chao MP, Majeti R, Traver D, van Rooijen N, Weissman IL. CD47 is upregulated on circulating hematopoietic stem cells and leukemia cells to avoid phagocytosis. Cell. 2009;138(2):271–85.PubMedPubMedCentralCrossRef Jaiswal S, Jamieson CH, Pang WW, Park CY, Chao MP, Majeti R, Traver D, van Rooijen N, Weissman IL. CD47 is upregulated on circulating hematopoietic stem cells and leukemia cells to avoid phagocytosis. Cell. 2009;138(2):271–85.PubMedPubMedCentralCrossRef
82.
go back to reference Vonderheide RH. CD47 blockade as another immune checkpoint therapy for cancer. Nat Med. 2015;21(10):1122–3.PubMedCrossRef Vonderheide RH. CD47 blockade as another immune checkpoint therapy for cancer. Nat Med. 2015;21(10):1122–3.PubMedCrossRef
83.
go back to reference Veillette A, Chen J. SIRPα–CD47 immune checkpoint blockade in anticancer therapy. Trends Immunol. 2018;39(3):173–84.PubMedCrossRef Veillette A, Chen J. SIRPα–CD47 immune checkpoint blockade in anticancer therapy. Trends Immunol. 2018;39(3):173–84.PubMedCrossRef
84.
go back to reference Pan Y, Lu F, Fei Q, Yu X, Xiong P, Yu X, Dang Y, Hou Z, Lin W, Lin X. Single-cell RNA sequencing reveals compartmental remodeling of tumor-infiltrating immune cells induced by anti-CD47 targeting in pancreatic cancer. J Hematol Oncol. 2019;12(1):1–18.CrossRef Pan Y, Lu F, Fei Q, Yu X, Xiong P, Yu X, Dang Y, Hou Z, Lin W, Lin X. Single-cell RNA sequencing reveals compartmental remodeling of tumor-infiltrating immune cells induced by anti-CD47 targeting in pancreatic cancer. J Hematol Oncol. 2019;12(1):1–18.CrossRef
85.
go back to reference Zhang W, Huang Q, Xiao W, Zhao Y, Pi J, Xu H, Zhao H, Xu J, Evans CE, Jin H. Advances in anti-tumor treatments targeting the CD47/SIRPα axis. Front Immunol 2020:18. Zhang W, Huang Q, Xiao W, Zhao Y, Pi J, Xu H, Zhao H, Xu J, Evans CE, Jin H. Advances in anti-tumor treatments targeting the CD47/SIRPα axis. Front Immunol 2020:18.
86.
go back to reference Kuo TC, Chen A, Harrabi O, Sockolosky JT, Zhang A, Sangalang E, Doyle LV, Kauder SE, Fontaine D, Bollini S, et al. Targeting the myeloid checkpoint receptor SIRPα potentiates innate and adaptive immune responses to promote anti-tumor activity. J Hematol Oncol. 2020;13(1):160.PubMedPubMedCentralCrossRef Kuo TC, Chen A, Harrabi O, Sockolosky JT, Zhang A, Sangalang E, Doyle LV, Kauder SE, Fontaine D, Bollini S, et al. Targeting the myeloid checkpoint receptor SIRPα potentiates innate and adaptive immune responses to promote anti-tumor activity. J Hematol Oncol. 2020;13(1):160.PubMedPubMedCentralCrossRef
87.
go back to reference Manna PP, Dimitry J, Oldenborg P-A, Frazier WA. CD47 augments Fas/CD95-mediated apoptosis. J Biol Chem. 2005;280(33):29637–44.PubMedCrossRef Manna PP, Dimitry J, Oldenborg P-A, Frazier WA. CD47 augments Fas/CD95-mediated apoptosis. J Biol Chem. 2005;280(33):29637–44.PubMedCrossRef
88.
go back to reference Mangelberger D, Augsberger C, Landgraf K, Heitmüller C, Steidl S. Blockade of the CD47/SIRPα checkpoint potentiates the anti-tumor efficacy of tafasitamab. Blood. 2020;136:11–2.CrossRef Mangelberger D, Augsberger C, Landgraf K, Heitmüller C, Steidl S. Blockade of the CD47/SIRPα checkpoint potentiates the anti-tumor efficacy of tafasitamab. Blood. 2020;136:11–2.CrossRef
89.
go back to reference Lin GH, Chai V, Lee V, Dodge K, Truong T, Wong M, Johnson LD, Pang X, Petrova PS, Uger RA. SIRPαFc, a CD47-blocking cancer immunotherapeutic, triggers phagocytosis of lymphoma cells by both classically (M1) and alternatively (M2) activated macrophages. AACR New Orleans 2016. Lin GH, Chai V, Lee V, Dodge K, Truong T, Wong M, Johnson LD, Pang X, Petrova PS, Uger RA. SIRPαFc, a CD47-blocking cancer immunotherapeutic, triggers phagocytosis of lymphoma cells by both classically (M1) and alternatively (M2) activated macrophages. AACR New Orleans 2016.
90.
go back to reference Liu X, Pu Y, Cron K, Deng L, Kline J, Frazier WA, Xu H, Peng H, Fu Y-X, Xu MM. CD47 blockade triggers T cell–mediated destruction of immunogenic tumors. Nat Med. 2015;21(10):1209–15.PubMedPubMedCentralCrossRef Liu X, Pu Y, Cron K, Deng L, Kline J, Frazier WA, Xu H, Peng H, Fu Y-X, Xu MM. CD47 blockade triggers T cell–mediated destruction of immunogenic tumors. Nat Med. 2015;21(10):1209–15.PubMedPubMedCentralCrossRef
91.
go back to reference Deuse T, Hu X, Agbor-Enoh S, Jang MK, Alawi M, Saygi C, Gravina A, Tediashvili G, Nguyen VQ, Liu Y. The SIRPα–CD47 immune checkpoint in NK cells. J Exp Med 2021;218(3). Deuse T, Hu X, Agbor-Enoh S, Jang MK, Alawi M, Saygi C, Gravina A, Tediashvili G, Nguyen VQ, Liu Y. The SIRPα–CD47 immune checkpoint in NK cells. J Exp Med 2021;218(3).
92.
go back to reference Hou J-Z, Ye JC, Pu JJ, Liu H, Ding W, Zheng H, Liu D. Novel agents and regimens for hematological malignancies: recent updates from 2020 ASH annual meeting. J Hematol Oncol. 2021;14(1):1–25.CrossRef Hou J-Z, Ye JC, Pu JJ, Liu H, Ding W, Zheng H, Liu D. Novel agents and regimens for hematological malignancies: recent updates from 2020 ASH annual meeting. J Hematol Oncol. 2021;14(1):1–25.CrossRef
94.
go back to reference Zeidan AM, DeAngelo DJ, Palmer JM, Seet CS, Tallman MS, Wei X, Li YF, Hock N, Burgess MR, Hege K. A phase I study of CC-90002, a monoclonal antibody targeting CD47, in patients with relapsed and/or refractory (R/R) acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS): final results. Blood. 2019;134:1320.CrossRef Zeidan AM, DeAngelo DJ, Palmer JM, Seet CS, Tallman MS, Wei X, Li YF, Hock N, Burgess MR, Hege K. A phase I study of CC-90002, a monoclonal antibody targeting CD47, in patients with relapsed and/or refractory (R/R) acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS): final results. Blood. 2019;134:1320.CrossRef
95.
go back to reference Zeidan AM, DeAngelo DJ, Palmer J, Seet CS, Tallman MS, Wei X, Raymon H, Sriraman P, Kopytek S, Bewersdorf JP, et al. Phase 1 study of anti-CD47 monoclonal antibody CC-90002 in patients with relapsed/refractory acute myeloid leukemia and high-risk myelodysplastic syndromes. Ann Hematol. 2022;101(3):557–69.PubMedCrossRef Zeidan AM, DeAngelo DJ, Palmer J, Seet CS, Tallman MS, Wei X, Raymon H, Sriraman P, Kopytek S, Bewersdorf JP, et al. Phase 1 study of anti-CD47 monoclonal antibody CC-90002 in patients with relapsed/refractory acute myeloid leukemia and high-risk myelodysplastic syndromes. Ann Hematol. 2022;101(3):557–69.PubMedCrossRef
96.
go back to reference Maute R, Xu J, Weissman IL. CD47–SIRPα-targeted therapeutics: status and prospects. Immuno-Oncol Technol 2022;13. Maute R, Xu J, Weissman IL. CD47–SIRPα-targeted therapeutics: status and prospects. Immuno-Oncol Technol 2022;13.
97.
go back to reference Haddad F, Daver N. Targeting CD47/SIRPα in acute myeloid leukemia and myelodysplastic syndrome: preclinical and clinical developments of magrolimab. J Immunother Precis Oncol. 2021;4(2):67–71.PubMedPubMedCentralCrossRef Haddad F, Daver N. Targeting CD47/SIRPα in acute myeloid leukemia and myelodysplastic syndrome: preclinical and clinical developments of magrolimab. J Immunother Precis Oncol. 2021;4(2):67–71.PubMedPubMedCentralCrossRef
98.
go back to reference Chen JY, Johnson L, McKenna KM, Choi TS, Duan J, Feng D, Tsai JM, Garcia-Martin N, Sompalli K, Maute R et al. Impact of magrolimab treatment in combination with azacitidine on red blood cells in patients with higher-risk myelodysplastic syndrome (HR-MDS). J Clin Oncol 2022;40(16_suppl):7054–7054. Chen JY, Johnson L, McKenna KM, Choi TS, Duan J, Feng D, Tsai JM, Garcia-Martin N, Sompalli K, Maute R et al. Impact of magrolimab treatment in combination with azacitidine on red blood cells in patients with higher-risk myelodysplastic syndrome (HR-MDS). J Clin Oncol 2022;40(16_suppl):7054–7054.
99.
go back to reference Sallman DA, Asch AS, Al Malki MM, Lee DJ, Donnellan WB, Marcucci G, Kambhampati S, Daver NG, Garcia-Manero G, Komrokji RS. The first-in-class anti-CD47 antibody magrolimab (5F9) in combination with azacitidine is effective in MDS and AML patients: ongoing phase 1b results. Blood. 2019;134:569.CrossRef Sallman DA, Asch AS, Al Malki MM, Lee DJ, Donnellan WB, Marcucci G, Kambhampati S, Daver NG, Garcia-Manero G, Komrokji RS. The first-in-class anti-CD47 antibody magrolimab (5F9) in combination with azacitidine is effective in MDS and AML patients: ongoing phase 1b results. Blood. 2019;134:569.CrossRef
100.
go back to reference Sallman DA, Al Malki M, Asch AS, Lee DJ, Kambhampati S, Donnellan WB, Bradley TJ, Vyas P, Jeyakumar D, Marcucci G. Tolerability and efficacy of the first-in-class anti-CD47 antibody magrolimab combined with azacitidine in MDS and AML patients: Phase Ib results. American Society of Clinical Oncology; 2020.CrossRef Sallman DA, Al Malki M, Asch AS, Lee DJ, Kambhampati S, Donnellan WB, Bradley TJ, Vyas P, Jeyakumar D, Marcucci G. Tolerability and efficacy of the first-in-class anti-CD47 antibody magrolimab combined with azacitidine in MDS and AML patients: Phase Ib results. American Society of Clinical Oncology; 2020.CrossRef
101.
go back to reference Daver NG, Vyas P, Kambhampati S, Malki MMA, Larson RA, Asch AS, Mannis GN, Chai-Ho W, Tanaka TN, Bradley TJ et al. Tolerability and efficacy of the first-in-class anti-CD47 antibody magrolimab combined with azacitidine in frontline TP53m AML patients: phase 1b results. J Clin Oncol 2022;40(16_suppl):7020–7020. Daver NG, Vyas P, Kambhampati S, Malki MMA, Larson RA, Asch AS, Mannis GN, Chai-Ho W, Tanaka TN, Bradley TJ et al. Tolerability and efficacy of the first-in-class anti-CD47 antibody magrolimab combined with azacitidine in frontline TP53m AML patients: phase 1b results. J Clin Oncol 2022;40(16_suppl):7020–7020.
102.
go back to reference Sallman DA, Malki MMA, Asch AS, Wang ES, Jurcic JG, Bradley TJ, Flinn IW, Pollyea DA, Kambhampati S, Tanaka TN et al. Magrolimab in combination with azacitidine for untreated higher-risk myelodysplastic syndromes (HR-MDS): 5F9005 phase 1b study results. J Clin Oncol 2022;40(16_suppl):7017–7017. Sallman DA, Malki MMA, Asch AS, Wang ES, Jurcic JG, Bradley TJ, Flinn IW, Pollyea DA, Kambhampati S, Tanaka TN et al. Magrolimab in combination with azacitidine for untreated higher-risk myelodysplastic syndromes (HR-MDS): 5F9005 phase 1b study results. J Clin Oncol 2022;40(16_suppl):7017–7017.
103.
go back to reference Kim TM, Lakhani N, Gainor J, Kamdar M, Fanning P, Squifflet P, Jin F, Wan H, Pons J, Randolph SS. A phase 1 study of ALX148, a CD47 blocker, in combination with rituximab in patients with non-Hodgkin lymphoma. Blood. 1953;2019:134. Kim TM, Lakhani N, Gainor J, Kamdar M, Fanning P, Squifflet P, Jin F, Wan H, Pons J, Randolph SS. A phase 1 study of ALX148, a CD47 blocker, in combination with rituximab in patients with non-Hodgkin lymphoma. Blood. 1953;2019:134.
104.
go back to reference Petrova PS, Viller NN, Wong M, Pang X, Lin GH, Dodge K, Chai V, Chen H, Lee V, House V. TTI-621 (SIRPαFc): a CD47-blocking innate immune checkpoint inhibitor with broad antitumor activity and minimal erythrocyte binding. Clin Cancer Res. 2017;23(4):1068–79.PubMedCrossRef Petrova PS, Viller NN, Wong M, Pang X, Lin GH, Dodge K, Chai V, Chen H, Lee V, House V. TTI-621 (SIRPαFc): a CD47-blocking innate immune checkpoint inhibitor with broad antitumor activity and minimal erythrocyte binding. Clin Cancer Res. 2017;23(4):1068–79.PubMedCrossRef
105.
go back to reference Ansell SM, Maris MB, Lesokhin AM, Chen RW, Flinn IW, Sawas A, Minden MD, Villa D, Pervical M-EM, Advani AS. Phase I study of the CD47 blocker TTI-621 in patients with relapsed or refractory hematologic malignancies. Clin Cancer Res. 2021;27(8):2190–9.PubMedCrossRef Ansell SM, Maris MB, Lesokhin AM, Chen RW, Flinn IW, Sawas A, Minden MD, Villa D, Pervical M-EM, Advani AS. Phase I study of the CD47 blocker TTI-621 in patients with relapsed or refractory hematologic malignancies. Clin Cancer Res. 2021;27(8):2190–9.PubMedCrossRef
106.
go back to reference Horwitz SM, Foran JM, Maris M, Lue JK, Sawas A, Okada C, Feldman TA, Sokol L, Mei M, Flinn IW, et al. Updates from ongoing, first-in-human phase 1 dose escalation and expansion study of TTI-621, a novel biologic targeting CD47, in patients with relapsed or refractory hematologic malignancies. Blood. 2021;138:2448.CrossRef Horwitz SM, Foran JM, Maris M, Lue JK, Sawas A, Okada C, Feldman TA, Sokol L, Mei M, Flinn IW, et al. Updates from ongoing, first-in-human phase 1 dose escalation and expansion study of TTI-621, a novel biologic targeting CD47, in patients with relapsed or refractory hematologic malignancies. Blood. 2021;138:2448.CrossRef
107.
go back to reference Querfeld C, Thompson JA, Taylor MH, DeSimone JA, Zain JM, Shustov AR, Johns C, McCann S, Lin GHY, Petrova PS, et al. Intralesional TTI-621, a novel biologic targeting the innate immune checkpoint CD47, in patients with relapsed or refractory mycosis fungoides or Sézary syndrome: a multicentre, phase 1 study. Lancet Haematol. 2021;8(11):e808–17.PubMedCrossRef Querfeld C, Thompson JA, Taylor MH, DeSimone JA, Zain JM, Shustov AR, Johns C, McCann S, Lin GHY, Petrova PS, et al. Intralesional TTI-621, a novel biologic targeting the innate immune checkpoint CD47, in patients with relapsed or refractory mycosis fungoides or Sézary syndrome: a multicentre, phase 1 study. Lancet Haematol. 2021;8(11):e808–17.PubMedCrossRef
108.
go back to reference Gholiha AR, Hollander P, Löf L, Glimelius I, Hedstrom G, Molin D, Hjalgrim H, Smedby KE, Hashemi J, Amini R-M, et al. Checkpoint CD47 expression in classical Hodgkin lymphoma. Br J Haematol. 2022;197(5):580–9.PubMedPubMedCentralCrossRef Gholiha AR, Hollander P, Löf L, Glimelius I, Hedstrom G, Molin D, Hjalgrim H, Smedby KE, Hashemi J, Amini R-M, et al. Checkpoint CD47 expression in classical Hodgkin lymphoma. Br J Haematol. 2022;197(5):580–9.PubMedPubMedCentralCrossRef
109.
go back to reference Sun M, Qi J, Zheng W, Song L, Jiang B, Wang Z, Huang C, Tian W, Qiu L. Preliminary results of a first-in-human phase I dtudy of IMM01, SIRPα Fc protein in patients with relapsed or refractory lymphoma. J Clin Oncol 2021;39(15_suppl):2550–2550. Sun M, Qi J, Zheng W, Song L, Jiang B, Wang Z, Huang C, Tian W, Qiu L. Preliminary results of a first-in-human phase I dtudy of IMM01, SIRPα Fc protein in patients with relapsed or refractory lymphoma. J Clin Oncol 2021;39(15_suppl):2550–2550.
110.
go back to reference Cabrales P, Carter C, Oronsky B, Reid T. Rrx-001 is a phase 3 small molecule dual inhibitor of CD47 and Sirpα with activity in multiple myeloma. Blood. 2018;132(Supplement 1):5623–5623.CrossRef Cabrales P, Carter C, Oronsky B, Reid T. Rrx-001 is a phase 3 small molecule dual inhibitor of CD47 and Sirpα with activity in multiple myeloma. Blood. 2018;132(Supplement 1):5623–5623.CrossRef
111.
go back to reference Wilson WC, Richards J, Puro RJ, Andrejeva G, Capoccia BJ, Donio MJ, Hiebsch RR, Chakraborty P, Sung V, Pereira DS. AO-176, a highly differentiated clinical stage anti-CD47 antibody, exerts potent anti-tumor activity in preclinical models of multiple myeloma as a single agent and in combination with approved therapeutics. Blood. 2020;136:3–4.CrossRef Wilson WC, Richards J, Puro RJ, Andrejeva G, Capoccia BJ, Donio MJ, Hiebsch RR, Chakraborty P, Sung V, Pereira DS. AO-176, a highly differentiated clinical stage anti-CD47 antibody, exerts potent anti-tumor activity in preclinical models of multiple myeloma as a single agent and in combination with approved therapeutics. Blood. 2020;136:3–4.CrossRef
112.
go back to reference Klausz K, Gehlert CL, Boje AS, Lustig M, Krohn S, Ahmed SM, Kellner C, Valerius T, Besse L, Besse A, et al. Blocking the Don’t Eat Me Signal (CD47-SIRPα Axis) to improve antibody-based immunotherapy of multiple myeloma. Blood. 2021;138:2684.CrossRef Klausz K, Gehlert CL, Boje AS, Lustig M, Krohn S, Ahmed SM, Kellner C, Valerius T, Besse L, Besse A, et al. Blocking the Don’t Eat Me Signal (CD47-SIRPα Axis) to improve antibody-based immunotherapy of multiple myeloma. Blood. 2021;138:2684.CrossRef
113.
go back to reference Sun J, Park C, Guenthner N, Gurley S, Zhang L, Lubben B, Adebayo O, Bash H, Chen Y, Maksimos M. Tumor-associated macrophages in multiple myeloma: advances in biology and therapy. J Immunother Cancer 2022;10(4). Sun J, Park C, Guenthner N, Gurley S, Zhang L, Lubben B, Adebayo O, Bash H, Chen Y, Maksimos M. Tumor-associated macrophages in multiple myeloma: advances in biology and therapy. J Immunother Cancer 2022;10(4).
114.
go back to reference Patel K, Orlowski RZ, Doucette K, Maris M, Pianko MJ, Ramchandren R, Stevens DA, Vesole DH, Uger RA, Scheuber A et al. TTI-622–01: A phase 1a/1b dose-escalation and expansion trial of TTI-622 in patients with advanced hematologic malignancies, including multiple myeloma. J Clin Oncol 2022;40(16_suppl):TPS8071–TPS8071. Patel K, Orlowski RZ, Doucette K, Maris M, Pianko MJ, Ramchandren R, Stevens DA, Vesole DH, Uger RA, Scheuber A et al. TTI-622–01: A phase 1a/1b dose-escalation and expansion trial of TTI-622 in patients with advanced hematologic malignancies, including multiple myeloma. J Clin Oncol 2022;40(16_suppl):TPS8071–TPS8071.
115.
go back to reference Stadtmauer E, Karlin L, Weisel K, Gatt ME, Kansagra A, Monohan G, Yee A, Rockow-Magnone S, Cordero J, Hoffman D. 448 Lemzoparlimab (TJ011133), an anti-CD47 antibody, with/without dexamethasone plus anti-myeloma regimens for relapsed/refractory multiple myeloma: a phase 1b dose escalation and expansion study. In.: Journal for immunotherapy of cancer; 2021. Stadtmauer E, Karlin L, Weisel K, Gatt ME, Kansagra A, Monohan G, Yee A, Rockow-Magnone S, Cordero J, Hoffman D. 448 Lemzoparlimab (TJ011133), an anti-CD47 antibody, with/without dexamethasone plus anti-myeloma regimens for relapsed/refractory multiple myeloma: a phase 1b dose escalation and expansion study. In.: Journal for immunotherapy of cancer; 2021.
116.
go back to reference Force MT. Safety Concerns Prompt Pause of Magrolimab Trials. Cancer Discov. 2022;12(4):877–8.CrossRef Force MT. Safety Concerns Prompt Pause of Magrolimab Trials. Cancer Discov. 2022;12(4):877–8.CrossRef
117.
go back to reference Yu J, Song Y, Tian W. How to select IgG subclasses in developing anti-tumor therapeutic antibodies. J Hematol Oncol. 2020;13(1):1–10.CrossRef Yu J, Song Y, Tian W. How to select IgG subclasses in developing anti-tumor therapeutic antibodies. J Hematol Oncol. 2020;13(1):1–10.CrossRef
118.
go back to reference Asaadi Y, Jouneghani FF, Janani S, Rahbarizadeh F. A comprehensive comparison between camelid nanobodies and single chain variable fragments. Biomark Res. 2021;9(1):87.PubMedPubMedCentralCrossRef Asaadi Y, Jouneghani FF, Janani S, Rahbarizadeh F. A comprehensive comparison between camelid nanobodies and single chain variable fragments. Biomark Res. 2021;9(1):87.PubMedPubMedCentralCrossRef
119.
go back to reference Jain S, Van Scoyk A, Morgan EA, Matthews A, Stevenson K, Newton G, Powers F, Autio A, Louissaint A Jr, Pontini G. Targeted inhibition of CD47-SIRPα requires Fc-FcγR interactions to maximize activity in T-cell lymphomas. Blood. 2019;134(17):1430–40.PubMedPubMedCentralCrossRef Jain S, Van Scoyk A, Morgan EA, Matthews A, Stevenson K, Newton G, Powers F, Autio A, Louissaint A Jr, Pontini G. Targeted inhibition of CD47-SIRPα requires Fc-FcγR interactions to maximize activity in T-cell lymphomas. Blood. 2019;134(17):1430–40.PubMedPubMedCentralCrossRef
120.
go back to reference Feng M, Chen JY, Weissman-Tsukamoto R, Volkmer J-P, Ho PY, McKenna KM, Cheshier S, Zhang M, Guo N, Gip P. Macrophages eat cancer cells using their own calreticulin as a guide: roles of TLR and Btk. Proc Natl Acad Sci. 2015;112(7):2145–50.PubMedPubMedCentralCrossRef Feng M, Chen JY, Weissman-Tsukamoto R, Volkmer J-P, Ho PY, McKenna KM, Cheshier S, Zhang M, Guo N, Gip P. Macrophages eat cancer cells using their own calreticulin as a guide: roles of TLR and Btk. Proc Natl Acad Sci. 2015;112(7):2145–50.PubMedPubMedCentralCrossRef
121.
go back to reference Chen J, Zhong M-C, Guo H, Davidson D, Mishel S, Lu Y, Rhee I, Pérez-Quintero L-A, Zhang S, Cruz-Munoz M-E. SLAMF7 is critical for phagocytosis of haematopoietic tumour cells via Mac-1 integrin. Nature. 2017;544(7651):493–7.PubMedPubMedCentralCrossRef Chen J, Zhong M-C, Guo H, Davidson D, Mishel S, Lu Y, Rhee I, Pérez-Quintero L-A, Zhang S, Cruz-Munoz M-E. SLAMF7 is critical for phagocytosis of haematopoietic tumour cells via Mac-1 integrin. Nature. 2017;544(7651):493–7.PubMedPubMedCentralCrossRef
123.
go back to reference Chen H, Yang Y, Deng Y, Wei F, Zhao Q, Liu Y, Liu Z, Yu B, Huang Z. Delivery of CD47 blocker SIRPα-Fc by CAR-T cells enhances antitumor efficacy. J Immunother Cancer 2022;10(2). Chen H, Yang Y, Deng Y, Wei F, Zhao Q, Liu Y, Liu Z, Yu B, Huang Z. Delivery of CD47 blocker SIRPα-Fc by CAR-T cells enhances antitumor efficacy. J Immunother Cancer 2022;10(2).
124.
125.
126.
127.
go back to reference Wu H, Liu J, Wang Z, Yuan W, Chen L. Prospects of antibodies targeting CD47 or CD24 in the treatment of glioblastoma. CNS Neurosci Ther. 2021;27(10):1105–17.PubMedPubMedCentralCrossRef Wu H, Liu J, Wang Z, Yuan W, Chen L. Prospects of antibodies targeting CD47 or CD24 in the treatment of glioblastoma. CNS Neurosci Ther. 2021;27(10):1105–17.PubMedPubMedCentralCrossRef
128.
go back to reference Yang R, Sun L, Li C-F, Wang Y-H, Yao J, Li H, Yan M, Chang W-C, Hsu J-M, Cha J-H. Galectin-9 interacts with PD-1 and TIM-3 to regulate T cell death and is a target for cancer immunotherapy. Nat Commun. 2021;12(1):1–17. Yang R, Sun L, Li C-F, Wang Y-H, Yao J, Li H, Yan M, Chang W-C, Hsu J-M, Cha J-H. Galectin-9 interacts with PD-1 and TIM-3 to regulate T cell death and is a target for cancer immunotherapy. Nat Commun. 2021;12(1):1–17.
129.
go back to reference Wang X, Wang G, Wang Z, Liu B, Han N, Li J, Lu C, Liu X, Zhang Q, Yang Q. PD-1-expressing B cells suppress CD4+ and CD8+ T cells via PD-1/PD-L1-dependent pathway. Mol Immunol. 2019;109:20–6.PubMedCrossRef Wang X, Wang G, Wang Z, Liu B, Han N, Li J, Lu C, Liu X, Zhang Q, Yang Q. PD-1-expressing B cells suppress CD4+ and CD8+ T cells via PD-1/PD-L1-dependent pathway. Mol Immunol. 2019;109:20–6.PubMedCrossRef
130.
go back to reference Hsu J, Hodgins JJ, Marathe M, Nicolai CJ, Bourgeois-Daigneault M-C, Trevino TN, Azimi CS, Scheer AK, Randolph HE, Thompson TW. Contribution of NK cells to immunotherapy mediated by PD-1/PD-L1 blockade. J Clin Investig. 2018;128(10):4654–68.PubMedPubMedCentralCrossRef Hsu J, Hodgins JJ, Marathe M, Nicolai CJ, Bourgeois-Daigneault M-C, Trevino TN, Azimi CS, Scheer AK, Randolph HE, Thompson TW. Contribution of NK cells to immunotherapy mediated by PD-1/PD-L1 blockade. J Clin Investig. 2018;128(10):4654–68.PubMedPubMedCentralCrossRef
131.
go back to reference Lim TS, Chew V, Sieow JL, Goh S, Yeong JP-S, Soon AL, Ricciardi-Castagnoli P. PD-1 expression on dendritic cells suppresses CD8+ T cell function and antitumor immunity. Oncoimmunology. 2016;5(3):e1085146.PubMedCrossRef Lim TS, Chew V, Sieow JL, Goh S, Yeong JP-S, Soon AL, Ricciardi-Castagnoli P. PD-1 expression on dendritic cells suppresses CD8+ T cell function and antitumor immunity. Oncoimmunology. 2016;5(3):e1085146.PubMedCrossRef
132.
go back to reference Reinke S, Bröckelmann PJ, Iaccarino I, Garcia-Marquez M, Borchmann S, Jochims F, Kotrova M, Pal K, Brüggemann M, Hartmann E. Tumor and microenvironment response but no cytotoxic T-cell activation in classic Hodgkin lymphoma treated with anti-PD1. Blood. 2020;136(25):2851–63.PubMedCrossRef Reinke S, Bröckelmann PJ, Iaccarino I, Garcia-Marquez M, Borchmann S, Jochims F, Kotrova M, Pal K, Brüggemann M, Hartmann E. Tumor and microenvironment response but no cytotoxic T-cell activation in classic Hodgkin lymphoma treated with anti-PD1. Blood. 2020;136(25):2851–63.PubMedCrossRef
133.
go back to reference Wang Y, Xiang Y, Xin VW, Wang X-W, Peng X-C, Liu X-Q, Wang D, Li N, Cheng J-T, Lyv Y-N, et al. Dendritic cell biology and its role in tumor immunotherapy. J Hematol Oncol. 2020;13(1):107.PubMedPubMedCentralCrossRef Wang Y, Xiang Y, Xin VW, Wang X-W, Peng X-C, Liu X-Q, Wang D, Li N, Cheng J-T, Lyv Y-N, et al. Dendritic cell biology and its role in tumor immunotherapy. J Hematol Oncol. 2020;13(1):107.PubMedPubMedCentralCrossRef
134.
go back to reference Colonna M, Samaridis J, Cella M, Angman L, Allen RL, O’Callaghan CA, Dunbar R, Ogg GS, Cerundolo V, Rolink A. Cutting edge: human myelomonocytic cells express an inhibitory receptor for classical and nonclassical MHC class I molecules. J Immunol. 1998;160(7):3096–100.PubMed Colonna M, Samaridis J, Cella M, Angman L, Allen RL, O’Callaghan CA, Dunbar R, Ogg GS, Cerundolo V, Rolink A. Cutting edge: human myelomonocytic cells express an inhibitory receptor for classical and nonclassical MHC class I molecules. J Immunol. 1998;160(7):3096–100.PubMed
135.
go back to reference Jones DC, Kosmoliaptsis V, Apps R, Lapaque N, Smith I, Kono A, Chang C, Boyle LH, Taylor CJ, Trowsdale J. HLA class I allelic sequence and conformation regulate leukocyte Ig-like receptor binding. J Immunol. 2011;186(5):2990–7.PubMedCrossRef Jones DC, Kosmoliaptsis V, Apps R, Lapaque N, Smith I, Kono A, Chang C, Boyle LH, Taylor CJ, Trowsdale J. HLA class I allelic sequence and conformation regulate leukocyte Ig-like receptor binding. J Immunol. 2011;186(5):2990–7.PubMedCrossRef
136.
go back to reference Hashambhoy-Ramsay Y, Spaulding V, Priess M, O’Malley K, Gostissa M, Stack E, Smith J, Willer M, Umiker B, Shaffer D. 217 Evaluating biomarkers of JTX-8064 (anti-LILRB2/ILT4 monoclonal antibody) in an ex vivo human tumor histoculture system to inform clinical development. In.: BMJ Specialist Journals; 2020. Hashambhoy-Ramsay Y, Spaulding V, Priess M, O’Malley K, Gostissa M, Stack E, Smith J, Willer M, Umiker B, Shaffer D. 217 Evaluating biomarkers of JTX-8064 (anti-LILRB2/ILT4 monoclonal antibody) in an ex vivo human tumor histoculture system to inform clinical development. In.: BMJ Specialist Journals; 2020.
137.
go back to reference Chen H, Chen Y, Deng M, John S, Gui X, Kansagra A, Chen W, Kim J, Lewis C, Wu G. Antagonistic anti-LILRB1 monoclonal antibody regulates antitumor functions of natural killer cells. J Immunother Cancer 2020;8(2). Chen H, Chen Y, Deng M, John S, Gui X, Kansagra A, Chen W, Kim J, Lewis C, Wu G. Antagonistic anti-LILRB1 monoclonal antibody regulates antitumor functions of natural killer cells. J Immunother Cancer 2020;8(2).
138.
go back to reference Pirruccello S, LeBien T. The human B cell-associated antigen CD24 is a single chain sialoglycoprotein. J Immunol. 1986;136(10):3779–84.PubMed Pirruccello S, LeBien T. The human B cell-associated antigen CD24 is a single chain sialoglycoprotein. J Immunol. 1986;136(10):3779–84.PubMed
139.
140.
141.
go back to reference Baumann P, Cremers N, Kroese F, Orend G, Chiquet-Ehrismann R, Uede T, Yagita H, Sleeman JP. CD24 expression causes the acquisition of multiple cellular properties associated with tumor growth and metastasis. Can Res. 2005;65(23):10783–93.CrossRef Baumann P, Cremers N, Kroese F, Orend G, Chiquet-Ehrismann R, Uede T, Yagita H, Sleeman JP. CD24 expression causes the acquisition of multiple cellular properties associated with tumor growth and metastasis. Can Res. 2005;65(23):10783–93.CrossRef
142.
go back to reference Ni Y-H, Zhao X, Wang W. CD24, a review of its role in tumor diagnosis, progression and therapy. Curr Gene Ther. 2020;20(2):109–26.PubMedCrossRef Ni Y-H, Zhao X, Wang W. CD24, a review of its role in tumor diagnosis, progression and therapy. Curr Gene Ther. 2020;20(2):109–26.PubMedCrossRef
144.
go back to reference Altevogt P, Sammar M, Hüser L, Kristiansen G. Novel insights into the function of CD24: a driving force in cancer. Int J Cancer. 2021;148(3):546–59.PubMedCrossRef Altevogt P, Sammar M, Hüser L, Kristiansen G. Novel insights into the function of CD24: a driving force in cancer. Int J Cancer. 2021;148(3):546–59.PubMedCrossRef
145.
go back to reference Aroldi A, Mauri M, Parma M, Terruzzi E, Fedele M, Perfetti P, Cocito F, Mologni L, Chiarle R, Piazza R, et al. CD24/Siglec-10 “Don’t Eat Me” signal blockade is a potential immunotherapeutic target in mantle-cell lymphoma. Blood. 2021;138:2276.CrossRef Aroldi A, Mauri M, Parma M, Terruzzi E, Fedele M, Perfetti P, Cocito F, Mologni L, Chiarle R, Piazza R, et al. CD24/Siglec-10 “Don’t Eat Me” signal blockade is a potential immunotherapeutic target in mantle-cell lymphoma. Blood. 2021;138:2276.CrossRef
146.
go back to reference Freile JÁ, Ustyanovska Avtenyuk N, Corrales MG, Lourens HJ, Huls G, van Meerten T, Cendrowicz E, Bremer E. CD24 Is a potential immunotherapeutic target for Mantle cell lymphoma. Biomedicines. 2022;10(5):1175.PubMedPubMedCentralCrossRef Freile JÁ, Ustyanovska Avtenyuk N, Corrales MG, Lourens HJ, Huls G, van Meerten T, Cendrowicz E, Bremer E. CD24 Is a potential immunotherapeutic target for Mantle cell lymphoma. Biomedicines. 2022;10(5):1175.PubMedPubMedCentralCrossRef
147.
go back to reference Allavena P, Anfray C, Ummarino A, Andón FT. Therapeutic manipulation of tumor-associated macrophages: Facts and hopes from a clinical and translational perspective. Clin Cancer Res. 2021;27(12):3291–7.PubMedCrossRef Allavena P, Anfray C, Ummarino A, Andón FT. Therapeutic manipulation of tumor-associated macrophages: Facts and hopes from a clinical and translational perspective. Clin Cancer Res. 2021;27(12):3291–7.PubMedCrossRef
148.
go back to reference Kumar S, Ramesh A, Kulkarni A. Targeting macrophages: a novel avenue for cancer drug discovery. Expert Opin Drug Discov. 2020;15(5):561–74.PubMedCrossRef Kumar S, Ramesh A, Kulkarni A. Targeting macrophages: a novel avenue for cancer drug discovery. Expert Opin Drug Discov. 2020;15(5):561–74.PubMedCrossRef
149.
go back to reference Sherr CJ, Rettenmier CW, Sacca R, Roussel MF, Look AT, Stanley ER. The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF 1. Cell. 1985;41(3):665–76.PubMedCrossRef Sherr CJ, Rettenmier CW, Sacca R, Roussel MF, Look AT, Stanley ER. The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF 1. Cell. 1985;41(3):665–76.PubMedCrossRef
150.
go back to reference Garceau V, Smith J, Paton IR, Davey M, Fares MA, Sester DP, Burt DW, Hume DA. Pivotal Advance: Avian colony-stimulating factor 1 (CSF-1), interleukin-34 (IL-34), and CSF-1 receptor genes and gene products. J Leukoc Biol. 2010;87(5):753–64.PubMedCrossRef Garceau V, Smith J, Paton IR, Davey M, Fares MA, Sester DP, Burt DW, Hume DA. Pivotal Advance: Avian colony-stimulating factor 1 (CSF-1), interleukin-34 (IL-34), and CSF-1 receptor genes and gene products. J Leukoc Biol. 2010;87(5):753–64.PubMedCrossRef
151.
go back to reference Wang T, Kono T, Monte MM, Kuse H, Costa MM, Korenaga H, Maehr T, Husain M, Sakai M, Secombes CJ. Identification of IL-34 in teleost fish: differential expression of rainbow trout IL-34, MCSF1 and MCSF2, ligands of the MCSF receptor. Mol Immunol. 2013;53(4):398–409.PubMedCrossRef Wang T, Kono T, Monte MM, Kuse H, Costa MM, Korenaga H, Maehr T, Husain M, Sakai M, Secombes CJ. Identification of IL-34 in teleost fish: differential expression of rainbow trout IL-34, MCSF1 and MCSF2, ligands of the MCSF receptor. Mol Immunol. 2013;53(4):398–409.PubMedCrossRef
152.
go back to reference Dai X-M, Ryan GR, Hapel AJ, Dominguez MG, Russell RG, Kapp S, Sylvestre V, Stanley ER. Targeted disruption of the mouse colony-stimulating factor 1 receptor gene results in osteopetrosis, mononuclear phagocyte deficiency, increased primitive progenitor cell frequencies, and reproductive defects. Blood. 2002;99(1):111–20.PubMedCrossRef Dai X-M, Ryan GR, Hapel AJ, Dominguez MG, Russell RG, Kapp S, Sylvestre V, Stanley ER. Targeted disruption of the mouse colony-stimulating factor 1 receptor gene results in osteopetrosis, mononuclear phagocyte deficiency, increased primitive progenitor cell frequencies, and reproductive defects. Blood. 2002;99(1):111–20.PubMedCrossRef
153.
go back to reference Pridans C, Raper A, Davis GM, Alves J, Sauter KA, Lefevre L, Regan T, Meek S, Sutherland L, Thomson AJ. Pleiotropic impacts of macrophage and microglial deficiency on development in rats with targeted mutation of the Csf1r locus. J Immunol. 2018;201(9):2683–99.PubMedPubMedCentralCrossRef Pridans C, Raper A, Davis GM, Alves J, Sauter KA, Lefevre L, Regan T, Meek S, Sutherland L, Thomson AJ. Pleiotropic impacts of macrophage and microglial deficiency on development in rats with targeted mutation of the Csf1r locus. J Immunol. 2018;201(9):2683–99.PubMedPubMedCentralCrossRef
154.
go back to reference Cannarile MA, Weisser M, Jacob W, Jegg A-M, Ries CH, Rüttinger D. Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy. J Immunother Cancer. 2017;5(1):1–13.CrossRef Cannarile MA, Weisser M, Jacob W, Jegg A-M, Ries CH, Rüttinger D. Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy. J Immunother Cancer. 2017;5(1):1–13.CrossRef
155.
go back to reference Wang Q, Lu Y, Li R, Jiang Y, Zheng Y, Qian J, Bi E, Zheng C, Hou J, Wang S. Therapeutic effects of CSF1R-blocking antibodies in multiple myeloma. Leukemia. 2018;32(1):176–83.PubMedCrossRef Wang Q, Lu Y, Li R, Jiang Y, Zheng Y, Qian J, Bi E, Zheng C, Hou J, Wang S. Therapeutic effects of CSF1R-blocking antibodies in multiple myeloma. Leukemia. 2018;32(1):176–83.PubMedCrossRef
156.
go back to reference Denny WA, Flanagan JU. Small-molecule CSF1R kinase inhibitors: review of patents 2015-present. Expert Opin Ther Pat. 2021;31(2):107–17.PubMedCrossRef Denny WA, Flanagan JU. Small-molecule CSF1R kinase inhibitors: review of patents 2015-present. Expert Opin Ther Pat. 2021;31(2):107–17.PubMedCrossRef
157.
go back to reference Smith CC, Levis MJ, Frankfurt O, Pagel JM, Roboz GJ, Stone RM, Wang ES, Severson PL, West BL, Le MH. A phase 1/2 study of the oral FLT3 inhibitor pexidartinib in relapsed/refractory FLT3-ITD–mutant acute myeloid leukemia. Blood Adv. 2020;4(8):1711–21.PubMedPubMedCentralCrossRef Smith CC, Levis MJ, Frankfurt O, Pagel JM, Roboz GJ, Stone RM, Wang ES, Severson PL, West BL, Le MH. A phase 1/2 study of the oral FLT3 inhibitor pexidartinib in relapsed/refractory FLT3-ITD–mutant acute myeloid leukemia. Blood Adv. 2020;4(8):1711–21.PubMedPubMedCentralCrossRef
158.
go back to reference Abeykoon JP, Lasho TL, Dasari S, Rech KL, Ranatunga WK, Manske MK, Tischer A, Ravindran A, Young JR, Tobin WO, et al. Sustained, complete response to pexidartinib in a patient with CSF1R-mutated Erdheim-Chester disease. Am J Hematol. 2022;97(3):293–302.PubMedCrossRef Abeykoon JP, Lasho TL, Dasari S, Rech KL, Ranatunga WK, Manske MK, Tischer A, Ravindran A, Young JR, Tobin WO, et al. Sustained, complete response to pexidartinib in a patient with CSF1R-mutated Erdheim-Chester disease. Am J Hematol. 2022;97(3):293–302.PubMedCrossRef
159.
go back to reference Sweeney T, Spurgeon SE, Tyner JW, Agarwal A, Ho H, Traer E, Lee P, Chantry D, Druker BJ, Loriaux M. Colony stimulating factor 1 receptor (CSF1R) as a potential novel therapeutic target in CLL. Blood. 2015;126(23):4439.CrossRef Sweeney T, Spurgeon SE, Tyner JW, Agarwal A, Ho H, Traer E, Lee P, Chantry D, Druker BJ, Loriaux M. Colony stimulating factor 1 receptor (CSF1R) as a potential novel therapeutic target in CLL. Blood. 2015;126(23):4439.CrossRef
160.
go back to reference Edwards DK, Watanabe-Smith K, Rofelty A, Damnernsawad A, Laderas T, Lamble A, Lind EF, Kaempf A, Mori M, Rosenberg M. CSF1R inhibitors exhibit antitumor activity in acute myeloid leukemia by blocking paracrine signals from support cells. Blood. 2019;133(6):588–99.PubMedPubMedCentralCrossRef Edwards DK, Watanabe-Smith K, Rofelty A, Damnernsawad A, Laderas T, Lamble A, Lind EF, Kaempf A, Mori M, Rosenberg M. CSF1R inhibitors exhibit antitumor activity in acute myeloid leukemia by blocking paracrine signals from support cells. Blood. 2019;133(6):588–99.PubMedPubMedCentralCrossRef
161.
go back to reference Ries CH, Hoves S, Cannarile MA, Rüttinger D. CSF-1/CSF-1R targeting agents in clinical development for cancer therapy. Curr Opin Pharmacol. 2015;23:45–51.PubMedCrossRef Ries CH, Hoves S, Cannarile MA, Rüttinger D. CSF-1/CSF-1R targeting agents in clinical development for cancer therapy. Curr Opin Pharmacol. 2015;23:45–51.PubMedCrossRef
162.
go back to reference von Tresckow B, Morschhauser F, Ribrag V, Topp MS, Chien C, Seetharam S, Aquino R, Kotoulek S, de Boer CJ, Engert A. An open-label, multicenter, phase I/II study of JNJ-40346527, a CSF-1R inhibitor, in patients with relapsed or refractory Hodgkin lymphoma. Clin Cancer Res. 2015;21(8):1843–50.CrossRef von Tresckow B, Morschhauser F, Ribrag V, Topp MS, Chien C, Seetharam S, Aquino R, Kotoulek S, de Boer CJ, Engert A. An open-label, multicenter, phase I/II study of JNJ-40346527, a CSF-1R inhibitor, in patients with relapsed or refractory Hodgkin lymphoma. Clin Cancer Res. 2015;21(8):1843–50.CrossRef
163.
go back to reference Cassier PA, Italiano A, Gomez-Roca CA, Le Tourneau C, Toulmonde M, Cannarile MA, Ries C, Brillouet A, Müller C, Jegg A-M. CSF1R inhibition with emactuzumab in locally advanced diffuse-type tenosynovial giant cell tumours of the soft tissue: a dose-escalation and dose-expansion phase 1 study. Lancet Oncol. 2015;16(8):949–56.PubMedCrossRef Cassier PA, Italiano A, Gomez-Roca CA, Le Tourneau C, Toulmonde M, Cannarile MA, Ries C, Brillouet A, Müller C, Jegg A-M. CSF1R inhibition with emactuzumab in locally advanced diffuse-type tenosynovial giant cell tumours of the soft tissue: a dose-escalation and dose-expansion phase 1 study. Lancet Oncol. 2015;16(8):949–56.PubMedCrossRef
164.
go back to reference Papadopoulos KP, Gluck L, Martin LP, Olszanski AJ, Tolcher AW, Ngarmchamnanrith G, Rasmussen E, Amore BM, Nagorsen D, Hill JS. First-in-human study of AMG 820, a monoclonal anti-colony-stimulating factor 1 receptor antibody, in patients with advanced solid tumors. Clin Cancer Res. 2017;23(19):5703–10.PubMedCrossRef Papadopoulos KP, Gluck L, Martin LP, Olszanski AJ, Tolcher AW, Ngarmchamnanrith G, Rasmussen E, Amore BM, Nagorsen D, Hill JS. First-in-human study of AMG 820, a monoclonal anti-colony-stimulating factor 1 receptor antibody, in patients with advanced solid tumors. Clin Cancer Res. 2017;23(19):5703–10.PubMedCrossRef
165.
go back to reference Korkosz M, Bukowska-Strakova K, Sadis S, Grodzicki T, Siedlar M. Monoclonal antibodies against macrophage colony-stimulating factor diminish the number of circulating intermediate and nonclassical (CD14++ CD16+/CD14+ CD16++) monocytes in rheumatoid arthritis patient. Blood. 2012;119(22):5329–30.PubMedCrossRef Korkosz M, Bukowska-Strakova K, Sadis S, Grodzicki T, Siedlar M. Monoclonal antibodies against macrophage colony-stimulating factor diminish the number of circulating intermediate and nonclassical (CD14++ CD16+/CD14+ CD16++) monocytes in rheumatoid arthritis patient. Blood. 2012;119(22):5329–30.PubMedCrossRef
167.
go back to reference Ginhoux F, Guilliams M. Tissue-resident macrophage ontogeny and homeostasis. Immunity. 2016;44(3):439–49.PubMedCrossRef Ginhoux F, Guilliams M. Tissue-resident macrophage ontogeny and homeostasis. Immunity. 2016;44(3):439–49.PubMedCrossRef
168.
go back to reference Bian Z, Gong Y, Huang T, Lee CZ, Bian L, Bai Z, Shi H, Zeng Y, Liu C, He J. Deciphering human macrophage development at single-cell resolution. Nature. 2020;582(7813):571–6.PubMedCrossRef Bian Z, Gong Y, Huang T, Lee CZ, Bian L, Bai Z, Shi H, Zeng Y, Liu C, He J. Deciphering human macrophage development at single-cell resolution. Nature. 2020;582(7813):571–6.PubMedCrossRef
169.
go back to reference Pathria P, Louis TL, Varner JA. Targeting tumor-associated macrophages in cancer. Trends Immunol. 2019;40(4):310–27.PubMedCrossRef Pathria P, Louis TL, Varner JA. Targeting tumor-associated macrophages in cancer. Trends Immunol. 2019;40(4):310–27.PubMedCrossRef
170.
go back to reference Lin Y, Xu J, Lan H. Tumor-associated macrophages in tumor metastasis: biological roles and clinical therapeutic applications. J Hematol Oncol. 2019;12(1):1–16.CrossRef Lin Y, Xu J, Lan H. Tumor-associated macrophages in tumor metastasis: biological roles and clinical therapeutic applications. J Hematol Oncol. 2019;12(1):1–16.CrossRef
171.
go back to reference Quail DF, Joyce JA. Molecular pathways: deciphering mechanisms of resistance to macrophage-targeted therapies. Clin Cancer Res. 2017;23(4):876–84.PubMedCrossRef Quail DF, Joyce JA. Molecular pathways: deciphering mechanisms of resistance to macrophage-targeted therapies. Clin Cancer Res. 2017;23(4):876–84.PubMedCrossRef
172.
go back to reference Zhang B, Li W, Fan D, Tian W, Zhou J, Ji Z, Song Y. Advances in the study of CD47‐based bispecific antibody in cancer immunotherapy. Immunology 2022. Zhang B, Li W, Fan D, Tian W, Zhou J, Ji Z, Song Y. Advances in the study of CD47‐based bispecific antibody in cancer immunotherapy. Immunology 2022.
173.
go back to reference Dahlén E, Veitonmäki N, Norlén P. Bispecific antibodies in cancer immunotherapy. Therap Adv Vaccines Immunother. 2018;6(1):3–17.CrossRef Dahlén E, Veitonmäki N, Norlén P. Bispecific antibodies in cancer immunotherapy. Therap Adv Vaccines Immunother. 2018;6(1):3–17.CrossRef
174.
go back to reference Tian W, Li S, Chen D, Liang G, Zhang L, Zhang W, Tu X, Peng L, Weng J, Zhao G. Preclinical development of a bispecific antibody-trap selectively targeting CD47 and CD20 for the treatment of B cell lineage cancer. In. AACR; 2019. Tian W, Li S, Chen D, Liang G, Zhang L, Zhang W, Tu X, Peng L, Weng J, Zhao G. Preclinical development of a bispecific antibody-trap selectively targeting CD47 and CD20 for the treatment of B cell lineage cancer. In. AACR; 2019.
175.
go back to reference Normant E, Ribeiro ML, Profitos-Peleja N, Blecua P, Reyes-Garau D, Santos JC, Armengol M, Fernández-Serrano M, Miskin HP, Roue G. The ublituximab-umbralisib (U2) drug regimen potentiates the activity of the novel CD47-CD19 bispecific antibody, TG-1801, through the activation of the G protein-coupled receptor EBI2/GPR183. Blood. 2021;138:1196.CrossRef Normant E, Ribeiro ML, Profitos-Peleja N, Blecua P, Reyes-Garau D, Santos JC, Armengol M, Fernández-Serrano M, Miskin HP, Roue G. The ublituximab-umbralisib (U2) drug regimen potentiates the activity of the novel CD47-CD19 bispecific antibody, TG-1801, through the activation of the G protein-coupled receptor EBI2/GPR183. Blood. 2021;138:1196.CrossRef
176.
go back to reference Feng R, Zhao H, Xu J, Shen C. CD47: the next checkpoint target for cancer immunotherapy. Crit Rev Oncol Hematol. 2020;152: 103014.PubMedCrossRef Feng R, Zhao H, Xu J, Shen C. CD47: the next checkpoint target for cancer immunotherapy. Crit Rev Oncol Hematol. 2020;152: 103014.PubMedCrossRef
177.
go back to reference Gozlan YM, Hilgendorf S, Aronin A, Sagiv Y, Ben-gigi-Tamir L, Amsili S, Tamir A, Pecker I, Greenwald S, Chajut A. Abstract A076: DSP107—A novel SIRPα-4–1BBL dual signaling protein (DSP) for cancer immunotherapy. In.: AACR; 2019. Gozlan YM, Hilgendorf S, Aronin A, Sagiv Y, Ben-gigi-Tamir L, Amsili S, Tamir A, Pecker I, Greenwald S, Chajut A. Abstract A076: DSP107—A novel SIRPα-4–1BBL dual signaling protein (DSP) for cancer immunotherapy. In.: AACR; 2019.
178.
go back to reference Cendrowicz E, Jacob L, Greenwald S, Tamir A, Gozlan Y, Huls G, Foley-Comer A, Pereg Y, Chajut A, Peled A. DSP107, a novel bi-functional fusion protein that combines inhibition of CD47 with targeted activation of 4–1BB to trigger innate and adaptive anticancer immune responses. Blood. 2020;136:19–20.CrossRef Cendrowicz E, Jacob L, Greenwald S, Tamir A, Gozlan Y, Huls G, Foley-Comer A, Pereg Y, Chajut A, Peled A. DSP107, a novel bi-functional fusion protein that combines inhibition of CD47 with targeted activation of 4–1BB to trigger innate and adaptive anticancer immune responses. Blood. 2020;136:19–20.CrossRef
179.
go back to reference Cendrowicz E, Jacob L, Greenwald S, Tamir A, Pecker I, Tabakman R, Ghantous L, Tamir L, Kahn R, Avichzer J, et al. DSP107 combines inhibition of CD47/SIRPα axis with activation of 4–1BB to trigger anticancer immunity. J Exp Clin Cancer Res. 2022;41(1):97.PubMedPubMedCentralCrossRef Cendrowicz E, Jacob L, Greenwald S, Tamir A, Pecker I, Tabakman R, Ghantous L, Tamir L, Kahn R, Avichzer J, et al. DSP107 combines inhibition of CD47/SIRPα axis with activation of 4–1BB to trigger anticancer immunity. J Exp Clin Cancer Res. 2022;41(1):97.PubMedPubMedCentralCrossRef
180.
go back to reference Luke JJ, Saeed A, Bashir B, Shwartz Y, Tabakman R, Foley-Comer A, Jimeno A. Phase 1 dose escalation study of DSP107, a first-in-class CD47 and 4–1BB targeting multifunctional immune-recruitment protein, in patients with advanced solid tumors. J Clin Oncol 2022;40(16_suppl):2647–2647. Luke JJ, Saeed A, Bashir B, Shwartz Y, Tabakman R, Foley-Comer A, Jimeno A. Phase 1 dose escalation study of DSP107, a first-in-class CD47 and 4–1BB targeting multifunctional immune-recruitment protein, in patients with advanced solid tumors. J Clin Oncol 2022;40(16_suppl):2647–2647.
181.
go back to reference Cortes JE, de Lima M, Dombret H, Estey EH, Giralt SA, Montesinos P, Röllig C, Venditti A, Wang ES. Prevention, recognition, and management of adverse events associated with gemtuzumab ozogamicin use in acute myeloid leukemia. J Hematol Oncol. 2020;13(1):137.PubMedPubMedCentralCrossRef Cortes JE, de Lima M, Dombret H, Estey EH, Giralt SA, Montesinos P, Röllig C, Venditti A, Wang ES. Prevention, recognition, and management of adverse events associated with gemtuzumab ozogamicin use in acute myeloid leukemia. J Hematol Oncol. 2020;13(1):137.PubMedPubMedCentralCrossRef
182.
go back to reference Wang Y, Pan D, Huang C, Chen B, Li M, Zhou S, Wang L, Wu M, Wang X, Bian Y. Dose escalation PET imaging for safety and effective therapy dose optimization of a bispecific antibody. In: MAbs: 2020: Taylor & Francis; 2020;1748322. Wang Y, Pan D, Huang C, Chen B, Li M, Zhou S, Wang L, Wu M, Wang X, Bian Y. Dose escalation PET imaging for safety and effective therapy dose optimization of a bispecific antibody. In: MAbs: 2020: Taylor & Francis; 2020;1748322.
183.
go back to reference Ferlin W, Masternak K, Shang L. Selective CD47 targeting with a bispecific antibody. Cancer Immunol Immunother. 2021;70(4):1161–2.PubMedCrossRef Ferlin W, Masternak K, Shang L. Selective CD47 targeting with a bispecific antibody. Cancer Immunol Immunother. 2021;70(4):1161–2.PubMedCrossRef
185.
go back to reference Stefano S, Grandclement C, Dehilly E, Panagopoulou M, Martini E, Castillo R, Suere P, Pouleau B, Estoppey C, Frei J, et al. ISB 1442, a first-in-class CD38 and cd47 bispecific antibody innate cell modulator for the treatment of relapsed refractory multiple myeloma. Blood. 2021;138:73.CrossRef Stefano S, Grandclement C, Dehilly E, Panagopoulou M, Martini E, Castillo R, Suere P, Pouleau B, Estoppey C, Frei J, et al. ISB 1442, a first-in-class CD38 and cd47 bispecific antibody innate cell modulator for the treatment of relapsed refractory multiple myeloma. Blood. 2021;138:73.CrossRef
186.
go back to reference Marin-Acevedo JA, Kimbrough EO, Manochakian R, Zhao Y, Lou Y. Immunotherapies targeting stimulatory pathways and beyond. J Hematol Oncol. 2021;14(1):78.PubMedPubMedCentralCrossRef Marin-Acevedo JA, Kimbrough EO, Manochakian R, Zhao Y, Lou Y. Immunotherapies targeting stimulatory pathways and beyond. J Hematol Oncol. 2021;14(1):78.PubMedPubMedCentralCrossRef
187.
go back to reference Ochsenbein AF, Riether C, Bacher U, Müller R, Höpner S, Banz Y, Hinterbrandner M, Bargetzi M, Manz MG, Van Rompaey L, et al. Argx-110 targeting CD70, in combination with azacitidine, shows favorable safety profile and promising anti-leukemia activity in newly diagnosed AML patients in an ongoing phase 1/2 clinical trial. Blood. 2018;132:2680.CrossRef Ochsenbein AF, Riether C, Bacher U, Müller R, Höpner S, Banz Y, Hinterbrandner M, Bargetzi M, Manz MG, Van Rompaey L, et al. Argx-110 targeting CD70, in combination with azacitidine, shows favorable safety profile and promising anti-leukemia activity in newly diagnosed AML patients in an ongoing phase 1/2 clinical trial. Blood. 2018;132:2680.CrossRef
188.
go back to reference Bagot M, Maerevoet M, Zinzani PL, Offner F, Morschhauser F, Michot J-M, Ribrag V, Battistella M, Moins H, Calleri A, et al. Argx-110 for treatment of CD70-positive advanced cutaneous T-cell lymphoma in a phase 1/2 clinical trial. Blood. 2018;132:1627.CrossRef Bagot M, Maerevoet M, Zinzani PL, Offner F, Morschhauser F, Michot J-M, Ribrag V, Battistella M, Moins H, Calleri A, et al. Argx-110 for treatment of CD70-positive advanced cutaneous T-cell lymphoma in a phase 1/2 clinical trial. Blood. 2018;132:1627.CrossRef
189.
go back to reference Ring Nan G, Herndler-Brandstetter D, Weiskopf K, Shan L, Volkmer J-P, George Benson M, Lietzenmayer M, McKenna Kelly M, Naik Tejaswitha J, McCarty A, et al. Anti-SIRPα antibody immunotherapy enhances neutrophil and macrophage antitumor activity. Proc Natl Acad Sci. 2017;114(49):E10578–85.PubMedPubMedCentral Ring Nan G, Herndler-Brandstetter D, Weiskopf K, Shan L, Volkmer J-P, George Benson M, Lietzenmayer M, McKenna Kelly M, Naik Tejaswitha J, McCarty A, et al. Anti-SIRPα antibody immunotherapy enhances neutrophil and macrophage antitumor activity. Proc Natl Acad Sci. 2017;114(49):E10578–85.PubMedPubMedCentral
190.
go back to reference Xu S, Zhang M, Fang X, Meng J, Xing H, Yan D, Liu J, Yang Y, Wen T, Zhang W, et al. A novel CD123-targeted therapeutic peptide loaded by micellar delivery system combats refractory acute myeloid leukemia. J Hematol Oncol. 2021;14(1):193.PubMedPubMedCentralCrossRef Xu S, Zhang M, Fang X, Meng J, Xing H, Yan D, Liu J, Yang Y, Wen T, Zhang W, et al. A novel CD123-targeted therapeutic peptide loaded by micellar delivery system combats refractory acute myeloid leukemia. J Hematol Oncol. 2021;14(1):193.PubMedPubMedCentralCrossRef
191.
go back to reference Tahk S, Vick B, Hiller B, Schmitt S, Marcinek A, Perini ED, Leutbecher A, Augsberger C, Reischer A, Tast B, et al. SIRPα-αCD123 fusion antibodies targeting CD123 in conjunction with CD47 blockade enhance the clearance of AML-initiating cells. J Hematol Oncol. 2021;14(1):155.PubMedPubMedCentralCrossRef Tahk S, Vick B, Hiller B, Schmitt S, Marcinek A, Perini ED, Leutbecher A, Augsberger C, Reischer A, Tast B, et al. SIRPα-αCD123 fusion antibodies targeting CD123 in conjunction with CD47 blockade enhance the clearance of AML-initiating cells. J Hematol Oncol. 2021;14(1):155.PubMedPubMedCentralCrossRef
192.
go back to reference Tian Z, Liu M, Zhang Y, Wang X. Bispecific T cell engagers: an emerging therapy for management of hematologic malignancies. J Hematol Oncol. 2021;14(1):1–18.CrossRef Tian Z, Liu M, Zhang Y, Wang X. Bispecific T cell engagers: an emerging therapy for management of hematologic malignancies. J Hematol Oncol. 2021;14(1):1–18.CrossRef
193.
go back to reference Liu S, Lyu W, Lei Y, Tan S, Wu Z, Yin S, Zheng L, Zhuo Q, Wen Y, Wu D. Abstract 1868: a long acting bi-specific T cell engager differentially targeting CD47 positive malignant cells but not CD47 expressing healthy cells. Cancer Res 2021;81(13_Supplement):1868–1868. Liu S, Lyu W, Lei Y, Tan S, Wu Z, Yin S, Zheng L, Zhuo Q, Wen Y, Wu D. Abstract 1868: a long acting bi-specific T cell engager differentially targeting CD47 positive malignant cells but not CD47 expressing healthy cells. Cancer Res 2021;81(13_Supplement):1868–1868.
194.
go back to reference Garfall AL, June CH. Trispecific antibodies offer a third way forward for anticancer immunotherapy. Nature Publishing Group; 2019.CrossRef Garfall AL, June CH. Trispecific antibodies offer a third way forward for anticancer immunotherapy. Nature Publishing Group; 2019.CrossRef
195.
go back to reference Genard G, Lucas S, Michiels C. Reprogramming of tumor-associated macrophages with anticancer therapies: radiotherapy versus chemo-and immunotherapies. Front Immunol. 2017;8:828.PubMedPubMedCentralCrossRef Genard G, Lucas S, Michiels C. Reprogramming of tumor-associated macrophages with anticancer therapies: radiotherapy versus chemo-and immunotherapies. Front Immunol. 2017;8:828.PubMedPubMedCentralCrossRef
197.
go back to reference Huang L, Xu H, Peng G. TLR-mediated metabolic reprogramming in the tumor microenvironment: potential novel strategies for cancer immunotherapy. Cell Mol Immunol. 2018;15(5):428–37.PubMedPubMedCentralCrossRef Huang L, Xu H, Peng G. TLR-mediated metabolic reprogramming in the tumor microenvironment: potential novel strategies for cancer immunotherapy. Cell Mol Immunol. 2018;15(5):428–37.PubMedPubMedCentralCrossRef
198.
go back to reference Brunner JS, Vogel A, Lercher A, Caldera M, Korosec A, Puehringer M, Hofmann M, Hajto A, Kieler M, Garrido LQ. The PI3K pathway preserves metabolic health through MARCO-dependent lipid uptake by adipose tissue macrophages. Nat Metab. 2020;2(12):1427–42.PubMedCrossRef Brunner JS, Vogel A, Lercher A, Caldera M, Korosec A, Puehringer M, Hofmann M, Hajto A, Kieler M, Garrido LQ. The PI3K pathway preserves metabolic health through MARCO-dependent lipid uptake by adipose tissue macrophages. Nat Metab. 2020;2(12):1427–42.PubMedCrossRef
199.
go back to reference La Fleur L, Botling J, He F, Pelicano C, Zhou C, He C, Palano G, Mezheyeuski A, Micke P, Ravetch JV. Targeting MARCO and IL37R on immunosuppressive macrophages in lung cancer blocks regulatory T cells and supports cytotoxic lymphocyte function. Can Res. 2021;81(4):956–67.CrossRef La Fleur L, Botling J, He F, Pelicano C, Zhou C, He C, Palano G, Mezheyeuski A, Micke P, Ravetch JV. Targeting MARCO and IL37R on immunosuppressive macrophages in lung cancer blocks regulatory T cells and supports cytotoxic lymphocyte function. Can Res. 2021;81(4):956–67.CrossRef
200.
go back to reference Eisinger S, Sarhan D, Boura VF, Ibarlucea-Benitez I, Tyystjärvi S, Oliynyk G, Arsenian-Henriksson M, Lane D, Wikström SL, Kiessling R. Targeting a scavenger receptor on tumor-associated macrophages activates tumor cell killing by natural killer cells. Proc Natl Acad Sci. 2020;117(50):32005–16.PubMedPubMedCentralCrossRef Eisinger S, Sarhan D, Boura VF, Ibarlucea-Benitez I, Tyystjärvi S, Oliynyk G, Arsenian-Henriksson M, Lane D, Wikström SL, Kiessling R. Targeting a scavenger receptor on tumor-associated macrophages activates tumor cell killing by natural killer cells. Proc Natl Acad Sci. 2020;117(50):32005–16.PubMedPubMedCentralCrossRef
201.
go back to reference Georgoudaki A-M, Prokopec KE, Boura VF, Hellqvist E, Sohn S, Östling J, Dahan R, Harris RA, Rantalainen M, Klevebring D. Reprogramming tumor-associated macrophages by antibody targeting inhibits cancer progression and metastasis. Cell Rep. 2016;15(9):2000–11.PubMedCrossRef Georgoudaki A-M, Prokopec KE, Boura VF, Hellqvist E, Sohn S, Östling J, Dahan R, Harris RA, Rantalainen M, Klevebring D. Reprogramming tumor-associated macrophages by antibody targeting inhibits cancer progression and metastasis. Cell Rep. 2016;15(9):2000–11.PubMedCrossRef
202.
go back to reference Li F, Ravetch JV. Inhibitory Fcγ receptor engagement drives adjuvant and anti-tumor activities of agonistic CD40 antibodies. Science. 2011;333(6045):1030–4.PubMedPubMedCentralCrossRef Li F, Ravetch JV. Inhibitory Fcγ receptor engagement drives adjuvant and anti-tumor activities of agonistic CD40 antibodies. Science. 2011;333(6045):1030–4.PubMedPubMedCentralCrossRef
203.
go back to reference Guo R, Lü M, Cao F, Wu G, Gao F, Pang H, Li Y, Zhang Y, Xing H, Liang C. Single-cell map of diverse immune phenotypes in the acute myeloid leukemia microenvironment. Biomark Res. 2021;9(1):1–16.CrossRef Guo R, Lü M, Cao F, Wu G, Gao F, Pang H, Li Y, Zhang Y, Xing H, Liang C. Single-cell map of diverse immune phenotypes in the acute myeloid leukemia microenvironment. Biomark Res. 2021;9(1):1–16.CrossRef
205.
go back to reference Akilesh HM, Buechler MB, Duggan JM, Hahn WO, Matta B, Sun X, Gessay G, Whalen E, Mason M, Presnell SR. Chronic TLR7 and TLR9 signaling drives anemia via differentiation of specialized hemophagocytes. Science 2019;363(6423):eaao5213. Akilesh HM, Buechler MB, Duggan JM, Hahn WO, Matta B, Sun X, Gessay G, Whalen E, Mason M, Presnell SR. Chronic TLR7 and TLR9 signaling drives anemia via differentiation of specialized hemophagocytes. Science 2019;363(6423):eaao5213.
206.
go back to reference Mathé G, Amiel J, Schwarzenberg L, Schneider M, Cattan A, Schlumberger JR, Hayat M, De Vassal F. Active immunotherapy for acute lymphoblastic leukaemia. The Lancet. 1969;293(7597):697–9.CrossRef Mathé G, Amiel J, Schwarzenberg L, Schneider M, Cattan A, Schlumberger JR, Hayat M, De Vassal F. Active immunotherapy for acute lymphoblastic leukaemia. The Lancet. 1969;293(7597):697–9.CrossRef
207.
go back to reference Weigel BJ, Cooley S, DeFor T, Weisdorf DJ, Panoskaltsis-Mortari A, Chen W, Blazar BR, Miller JS. Prolonged subcutaneous administration of 852A, a novel systemic toll-like receptor 7 agonist, to activate innate immune responses in patients with advanced hematologic malignancies. Am J Hematol. 2012;87(10):953–6.PubMedPubMedCentralCrossRef Weigel BJ, Cooley S, DeFor T, Weisdorf DJ, Panoskaltsis-Mortari A, Chen W, Blazar BR, Miller JS. Prolonged subcutaneous administration of 852A, a novel systemic toll-like receptor 7 agonist, to activate innate immune responses in patients with advanced hematologic malignancies. Am J Hematol. 2012;87(10):953–6.PubMedPubMedCentralCrossRef
208.
go back to reference Ronsley R, Kariminia A, Ng B, Mostafavi S, Reid G, Subrt P, Hijiya N, Schultz KR. The TLR9 agonist (GNKG168) induces a unique immune activation pattern in vivo in children with minimal residual disease positive acute leukemia: Results of the TACL T2009–008 phase I study. Pediatr Hematol Oncol. 2019;36(8):468–81.PubMedCrossRef Ronsley R, Kariminia A, Ng B, Mostafavi S, Reid G, Subrt P, Hijiya N, Schultz KR. The TLR9 agonist (GNKG168) induces a unique immune activation pattern in vivo in children with minimal residual disease positive acute leukemia: Results of the TACL T2009–008 phase I study. Pediatr Hematol Oncol. 2019;36(8):468–81.PubMedCrossRef
209.
go back to reference Miyanishi M, Tada K, Koike M, Uchiyama Y, Kitamura T, Nagata S. Identification of Tim4 as a phosphatidylserine receptor. Nature. 2007;450(7168):435–9.PubMedCrossRef Miyanishi M, Tada K, Koike M, Uchiyama Y, Kitamura T, Nagata S. Identification of Tim4 as a phosphatidylserine receptor. Nature. 2007;450(7168):435–9.PubMedCrossRef
210.
go back to reference Xia H, Li S, Li X, Wang W, Bian Y, Wei S, Grove S, Wang W, Vatan L, Liu JR. Autophagic adaptation to oxidative stress alters peritoneal residential macrophage survival and ovarian cancer metastasis. JCI insight 2020;5(18). Xia H, Li S, Li X, Wang W, Bian Y, Wei S, Grove S, Wang W, Vatan L, Liu JR. Autophagic adaptation to oxidative stress alters peritoneal residential macrophage survival and ovarian cancer metastasis. JCI insight 2020;5(18).
211.
go back to reference Etzerodt A, Moulin M, Doktor TK, Delfini M, Mossadegh-Keller N, Bajenoff M, Sieweke MH, Moestrup SK, Auphan-Anezin N, Lawrence T. Tissue-resident macrophages in omentum promote metastatic spread of ovarian cancer. J Exp Med 2020;217(4). Etzerodt A, Moulin M, Doktor TK, Delfini M, Mossadegh-Keller N, Bajenoff M, Sieweke MH, Moestrup SK, Auphan-Anezin N, Lawrence T. Tissue-resident macrophages in omentum promote metastatic spread of ovarian cancer. J Exp Med 2020;217(4).
212.
go back to reference Casanova-Acebes M, Menéndez-Gutiérrez MP, Porcuna J, Álvarez-Errico D, Lavin Y, García A, Kobayashi S, Le Berichel J, Núñez V, Were F. RXRs control serous macrophage neonatal expansion and identity and contribute to ovarian cancer progression. Nat Commun. 2020;11(1):1–13.CrossRef Casanova-Acebes M, Menéndez-Gutiérrez MP, Porcuna J, Álvarez-Errico D, Lavin Y, García A, Kobayashi S, Le Berichel J, Núñez V, Were F. RXRs control serous macrophage neonatal expansion and identity and contribute to ovarian cancer progression. Nat Commun. 2020;11(1):1–13.CrossRef
213.
go back to reference Chow A, Schad S, Green MD, Hellmann MD, Allaj V, Ceglia N, Zago G, Shah NS, Sharma SK, Mattar M. Tim-4+ cavity-resident macrophages impair anti-tumor CD8+ T cell immunity. Cancer Cell 2021;39(7):973–988. e979. Chow A, Schad S, Green MD, Hellmann MD, Allaj V, Ceglia N, Zago G, Shah NS, Sharma SK, Mattar M. Tim-4+ cavity-resident macrophages impair anti-tumor CD8+ T cell immunity. Cancer Cell 2021;39(7):973–988. e979.
214.
go back to reference Sallman DA, Donnellan WB, Asch AS, Lee DJ, Al Malki M, Marcucci G, Pollyea DA, Kambhampati S, Komrokji RS, Van Elk J. The first-in-class anti-CD47 antibody Hu5F9-G4 is active and well tolerated alone or with azacitidine in AML and MDS patients: initial phase 1b results. American Society of Clinical Oncology; 2019. Sallman DA, Donnellan WB, Asch AS, Lee DJ, Al Malki M, Marcucci G, Pollyea DA, Kambhampati S, Komrokji RS, Van Elk J. The first-in-class anti-CD47 antibody Hu5F9-G4 is active and well tolerated alone or with azacitidine in AML and MDS patients: initial phase 1b results. American Society of Clinical Oncology; 2019.
215.
go back to reference Morrissey MA, Williamson AP, Steinbach AM, Roberts EW, Kern N, Headley MB, Vale RD. Chimeric antigen receptors that trigger phagocytosis. elife 2018;7:e36688. Morrissey MA, Williamson AP, Steinbach AM, Roberts EW, Kern N, Headley MB, Vale RD. Chimeric antigen receptors that trigger phagocytosis. elife 2018;7:e36688.
216.
go back to reference Chen Y, Yu Z, Tan X, Jiang H, Xu Z, Fang Y, Han D, Hong W, Wei W, Tu J. CAR-macrophage: a new immunotherapy candidate against solid tumors. Biomed Pharmacother. 2021;139: 111605.PubMedCrossRef Chen Y, Yu Z, Tan X, Jiang H, Xu Z, Fang Y, Han D, Hong W, Wei W, Tu J. CAR-macrophage: a new immunotherapy candidate against solid tumors. Biomed Pharmacother. 2021;139: 111605.PubMedCrossRef
217.
go back to reference Zhang W, Liu L, Su H, Liu Q, Shen J, Dai H, Zheng W, Lu Y, Zhang W, Bei Y. Chimeric antigen receptor macrophage therapy for breast tumours mediated by targeting the tumour extracellular matrix. Br J Cancer. 2019;121(10):837–45.PubMedPubMedCentralCrossRef Zhang W, Liu L, Su H, Liu Q, Shen J, Dai H, Zheng W, Lu Y, Zhang W, Bei Y. Chimeric antigen receptor macrophage therapy for breast tumours mediated by targeting the tumour extracellular matrix. Br J Cancer. 2019;121(10):837–45.PubMedPubMedCentralCrossRef
218.
go back to reference Kang M, Lee SH, Kwon M, Byun J, Kim D, Kim C, Koo S, Kwon SP, Moon S, Jung M, et al. Nanocomplex-mediated in vivo programming to chimeric antigen receptor-M1 macrophages for cancer therapy. Adv Mater. 2021;33(43):2103258.CrossRef Kang M, Lee SH, Kwon M, Byun J, Kim D, Kim C, Koo S, Kwon SP, Moon S, Jung M, et al. Nanocomplex-mediated in vivo programming to chimeric antigen receptor-M1 macrophages for cancer therapy. Adv Mater. 2021;33(43):2103258.CrossRef
220.
Metadata
Title
Targeting macrophages in hematological malignancies: recent advances and future directions
Authors
Wei Li
Fang Wang
Rongqun Guo
Zhilei Bian
Yongping Song
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2022
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-022-01328-x

Other articles of this Issue 1/2022

Journal of Hematology & Oncology 1/2022 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine