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Published in: BMC Cancer 1/2024

Open Access 01-12-2024 | Lung Cancer | Research

Co-expression of IL-21-Enhanced NKG2D CAR-NK cell therapy for lung cancer

Authors: Yan Zhang, Cong Zhang, Minghong He, Weipeng Xing, Rui Hou, Haijin Zhang

Published in: BMC Cancer | Issue 1/2024

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Abstract

Background

Adoptive cell therapy has achieved great success in treating hematological malignancies. However, the production of chimeric antigen receptor T (CAR-T) cell therapy still faces various difficulties. Natural killer (NK)-92 is a continuously expandable cell line and provides a promising alternative for patient’s own immune cells.

Methods

We established CAR-NK cells by co-expressing natural killer group 2 member D (NKG2D) and IL-21, and evaluated the efficacy of NKG2D-IL-21 CAR-NK cells in treating lung cancer in vitro and in vivo.

Results

Our data suggested that the expression of IL-21 effectively increased the cytotoxicity of NKG2D CAR-NK cells against lung cancer cells in a dose-dependent manner and suppressed tumor growth in vitro and in vivo. In addition, the proliferation of NKG2D-IL-21 CAR-NK cells were enhanced while the apoptosis and exhaustion of these cells were suppressed. Mechanistically, IL-21-mediated NKG2D CAR-NK cells function by activating AKT signaling pathway.

Conclusion

Our findings provide a novel option for treating lung cancer using NKG2D-IL-21 CAR-NK cell therapy.
Appendix
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Literature
1.
go back to reference Mendieta I, Rodríguez-Nieto M, Nuñez-Anita RE, Menchaca-Arredondo JL, García-Alcocer G, Berumen LC. Ultrastructural changes associated to the neuroendocrine transdifferentiation of the lung adenocarcinoma cell line A549. Acta Histochem. 2021;123(8):151797.PubMedCrossRef Mendieta I, Rodríguez-Nieto M, Nuñez-Anita RE, Menchaca-Arredondo JL, García-Alcocer G, Berumen LC. Ultrastructural changes associated to the neuroendocrine transdifferentiation of the lung adenocarcinoma cell line A549. Acta Histochem. 2021;123(8):151797.PubMedCrossRef
2.
go back to reference Jia Q, Xie B, Zhao Z, Huang L, Wei G, Ni T. Lung cancer cells expressing a shortened CDK16 3’UTR escape senescence through impaired mir-485-5p targeting. Mol Oncol. 2022;16(6):1347–64.PubMedCrossRef Jia Q, Xie B, Zhao Z, Huang L, Wei G, Ni T. Lung cancer cells expressing a shortened CDK16 3’UTR escape senescence through impaired mir-485-5p targeting. Mol Oncol. 2022;16(6):1347–64.PubMedCrossRef
3.
go back to reference Yang J, Hui Y, Zhang Y, Zhang M, Ji B, Tian G, Guo Y, Tang M, Li L, Guo B, et al. Application of circulating Tumor DNA as a Biomarker for Non-small Cell Lung Cancer. Front Oncol. 2021;11:725938.PubMedPubMedCentralCrossRef Yang J, Hui Y, Zhang Y, Zhang M, Ji B, Tian G, Guo Y, Tang M, Li L, Guo B, et al. Application of circulating Tumor DNA as a Biomarker for Non-small Cell Lung Cancer. Front Oncol. 2021;11:725938.PubMedPubMedCentralCrossRef
4.
go back to reference Song Z, Chen X, Shi Y, Huang R, Wang W, Zhu K, Lin S, Wang M, Tian G, Yang J, et al. Evaluating the potential of T cell receptor repertoires in Predicting the prognosis of Resectable Non-small Cell Lung cancers. Mol Ther Methods Clin Dev. 2020;18:73–83.PubMedPubMedCentralCrossRef Song Z, Chen X, Shi Y, Huang R, Wang W, Zhu K, Lin S, Wang M, Tian G, Yang J, et al. Evaluating the potential of T cell receptor repertoires in Predicting the prognosis of Resectable Non-small Cell Lung cancers. Mol Ther Methods Clin Dev. 2020;18:73–83.PubMedPubMedCentralCrossRef
5.
go back to reference Rotolo N, Cattoni M, D’Andria M, Cavanna L, Patrizio G, Imperatori A, Nicolini A. Comparison of an expiratory flow accelerator device versus positive expiratory pressure for tracheobronchial airway clearance after lung cancer lobectomy: a preliminary study. Physiotherapy. 2021;110:34–41.PubMedCrossRef Rotolo N, Cattoni M, D’Andria M, Cavanna L, Patrizio G, Imperatori A, Nicolini A. Comparison of an expiratory flow accelerator device versus positive expiratory pressure for tracheobronchial airway clearance after lung cancer lobectomy: a preliminary study. Physiotherapy. 2021;110:34–41.PubMedCrossRef
6.
go back to reference Chen Y, Chen C, Zhang X, He C, Zhao P, Li M, Fan T, Yan R, Lu Y, Lee RJ, et al. Platinum complexes of curcumin delivered by dual-responsive polymeric nanoparticles improve chemotherapeutic efficacy based on the enhanced anti-metastasis activity and reduce side effects. Acta Pharm Sinica B. 2020;10(6):1106–21.CrossRef Chen Y, Chen C, Zhang X, He C, Zhao P, Li M, Fan T, Yan R, Lu Y, Lee RJ, et al. Platinum complexes of curcumin delivered by dual-responsive polymeric nanoparticles improve chemotherapeutic efficacy based on the enhanced anti-metastasis activity and reduce side effects. Acta Pharm Sinica B. 2020;10(6):1106–21.CrossRef
7.
go back to reference Akamatsu H, Murakami E, Oyanagi J, Shibaki R, Kaki T, Takase E, Tanaka M, Harutani Y, Yamagata N, Okuda Y, et al. Immune-related adverse events by Immune checkpoint inhibitors significantly predict durable efficacy even in responders with Advanced Non-small Cell Lung Cancer. Oncologist. 2020;25(4):e679–83.PubMedCrossRef Akamatsu H, Murakami E, Oyanagi J, Shibaki R, Kaki T, Takase E, Tanaka M, Harutani Y, Yamagata N, Okuda Y, et al. Immune-related adverse events by Immune checkpoint inhibitors significantly predict durable efficacy even in responders with Advanced Non-small Cell Lung Cancer. Oncologist. 2020;25(4):e679–83.PubMedCrossRef
8.
go back to reference Meng Y, Lu C, Jin M, Xu J, Zeng X, Yang J. A weighted bilinear neural collaborative filtering approach for drug repositioning. Brief Bioinform. 2022;23(2):bbab581.PubMedCrossRef Meng Y, Lu C, Jin M, Xu J, Zeng X, Yang J. A weighted bilinear neural collaborative filtering approach for drug repositioning. Brief Bioinform. 2022;23(2):bbab581.PubMedCrossRef
9.
go back to reference Liu C, Wei D, Xiang J, Ren F, Huang L, Lang J, Tian G, Li Y, Yang J. An improved Anticancer Drug-Response Prediction based on an Ensemble Method integrating Matrix Completion and Ridge Regression. Mol Ther Nucleic Acids. 2020;21:676–86.PubMedPubMedCentralCrossRef Liu C, Wei D, Xiang J, Ren F, Huang L, Lang J, Tian G, Li Y, Yang J. An improved Anticancer Drug-Response Prediction based on an Ensemble Method integrating Matrix Completion and Ridge Regression. Mol Ther Nucleic Acids. 2020;21:676–86.PubMedPubMedCentralCrossRef
10.
go back to reference Fang W, Zhao S, Liang Y, Yang Y, Yang L, Dong X, Zhang L, Tang Y, Wang S, Yang Y, et al. Mutation variants and co-mutations as genomic modifiers of response to Afatinib in HER2-Mutant lung adenocarcinoma. Oncologist. 2020;25(3):e545–54.PubMedCrossRef Fang W, Zhao S, Liang Y, Yang Y, Yang L, Dong X, Zhang L, Tang Y, Wang S, Yang Y, et al. Mutation variants and co-mutations as genomic modifiers of response to Afatinib in HER2-Mutant lung adenocarcinoma. Oncologist. 2020;25(3):e545–54.PubMedCrossRef
11.
go back to reference Takayama K, Ichiki M, Matsumoto T, Ebi N, Akamine S, Tokunaga S, Yamada T, Uchino J, Nakanishi Y. Phase II Study on Biweekly Combination Therapy of Gemcitabine plus Carboplatin for the Treatment of Elderly Patients with Advanced Non-Small Cell Lung Cancer. The oncologist 2019. Takayama K, Ichiki M, Matsumoto T, Ebi N, Akamine S, Tokunaga S, Yamada T, Uchino J, Nakanishi Y. Phase II Study on Biweekly Combination Therapy of Gemcitabine plus Carboplatin for the Treatment of Elderly Patients with Advanced Non-Small Cell Lung Cancer. The oncologist 2019.
12.
go back to reference Liu H, Qiu C, Wang B, Bing P, Tian G, Zhang X, Ma J, He B, Yang J. Evaluating DNA methylation, Gene expression, somatic mutation, and their combinations in Inferring Tumor tissue-of-origin. Front Cell Dev Biol. 2021;9:619330.PubMedPubMedCentralCrossRef Liu H, Qiu C, Wang B, Bing P, Tian G, Zhang X, Ma J, He B, Yang J. Evaluating DNA methylation, Gene expression, somatic mutation, and their combinations in Inferring Tumor tissue-of-origin. Front Cell Dev Biol. 2021;9:619330.PubMedPubMedCentralCrossRef
13.
go back to reference He B, Lang J, Wang B, Liu X, Lu Q, He J, Gao W, Bing P, Tian G, Yang J. TOOme: a Novel Computational Framework to Infer Cancer tissue-of-origin by integrating both gene mutation and expression. Front Bioeng Biotechnol. 2020;8:394.PubMedPubMedCentralCrossRef He B, Lang J, Wang B, Liu X, Lu Q, He J, Gao W, Bing P, Tian G, Yang J. TOOme: a Novel Computational Framework to Infer Cancer tissue-of-origin by integrating both gene mutation and expression. Front Bioeng Biotechnol. 2020;8:394.PubMedPubMedCentralCrossRef
14.
go back to reference Brentjens RJ, Davila ML, Riviere I, Park J, Wang X, Cowell LG, Bartido S, Stefanski J, Taylor C, Olszewska M, et al. CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci Transl Med. 2013;5(177):177ra138.CrossRef Brentjens RJ, Davila ML, Riviere I, Park J, Wang X, Cowell LG, Bartido S, Stefanski J, Taylor C, Olszewska M, et al. CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci Transl Med. 2013;5(177):177ra138.CrossRef
15.
go back to reference Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, Chew A, Gonzalez VE, Zheng Z, Lacey SF, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014;371(16):1507–17.PubMedPubMedCentralCrossRef Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, Chew A, Gonzalez VE, Zheng Z, Lacey SF, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014;371(16):1507–17.PubMedPubMedCentralCrossRef
16.
go back to reference Ferrara JL, Levine JE, Reddy P, Holler E. Graft-versus-host disease. Lancet (London England). 2009;373(9674):1550–61.PubMedCrossRef Ferrara JL, Levine JE, Reddy P, Holler E. Graft-versus-host disease. Lancet (London England). 2009;373(9674):1550–61.PubMedCrossRef
17.
go back to reference Goulmy E. Human minor histocompatibility antigens: new concepts for marrow transplantation and adoptive immunotherapy. Immunol Rev. 1997;157:125–40.PubMedCrossRef Goulmy E. Human minor histocompatibility antigens: new concepts for marrow transplantation and adoptive immunotherapy. Immunol Rev. 1997;157:125–40.PubMedCrossRef
18.
go back to reference Yilmaz A, Cui H, Caligiuri MA, Yu J. Chimeric antigen receptor-engineered natural killer cells for cancer immunotherapy. J Hematol Oncol. 2020;13(1):168.PubMedPubMedCentralCrossRef Yilmaz A, Cui H, Caligiuri MA, Yu J. Chimeric antigen receptor-engineered natural killer cells for cancer immunotherapy. J Hematol Oncol. 2020;13(1):168.PubMedPubMedCentralCrossRef
19.
go back to reference Morvan MG, Lanier LL. NK cells and cancer: you can teach innate cells new tricks. Nat Rev Cancer. 2016;16(1):7–19.PubMedCrossRef Morvan MG, Lanier LL. NK cells and cancer: you can teach innate cells new tricks. Nat Rev Cancer. 2016;16(1):7–19.PubMedCrossRef
20.
go back to reference Simonetta F, Alvarez M, Negrin RS. Natural killer cells in Graft-versus-Host-Disease after allogeneic hematopoietic cell transplantation. Front Immunol. 2017;8:465.PubMedPubMedCentralCrossRef Simonetta F, Alvarez M, Negrin RS. Natural killer cells in Graft-versus-Host-Disease after allogeneic hematopoietic cell transplantation. Front Immunol. 2017;8:465.PubMedPubMedCentralCrossRef
21.
go back to reference Suck G, Odendahl M, Nowakowska P, Seidl C, Wels WS, Klingemann HG, Tonn T. NK-92: an ‘off-the-shelf therapeutic’ for adoptive natural killer cell-based cancer immunotherapy. Cancer Immunol Immunotherapy: CII. 2016;65(4):485–92.PubMedCrossRef Suck G, Odendahl M, Nowakowska P, Seidl C, Wels WS, Klingemann HG, Tonn T. NK-92: an ‘off-the-shelf therapeutic’ for adoptive natural killer cell-based cancer immunotherapy. Cancer Immunol Immunotherapy: CII. 2016;65(4):485–92.PubMedCrossRef
22.
go back to reference Hu Y, Tian ZG, Zhang C. Chimeric antigen receptor (CAR)-transduced natural killer cells in tumor immunotherapy. Acta Pharmacol Sin. 2018;39(2):167–76.PubMedCrossRef Hu Y, Tian ZG, Zhang C. Chimeric antigen receptor (CAR)-transduced natural killer cells in tumor immunotherapy. Acta Pharmacol Sin. 2018;39(2):167–76.PubMedCrossRef
23.
go back to reference Lapteva N, Szmania SM, van Rhee F, Rooney CM. Clinical grade purification and expansion of natural killer cells. Crit Rev Oncog. 2014;19(1–2):121–32.PubMedPubMedCentralCrossRef Lapteva N, Szmania SM, van Rhee F, Rooney CM. Clinical grade purification and expansion of natural killer cells. Crit Rev Oncog. 2014;19(1–2):121–32.PubMedPubMedCentralCrossRef
24.
go back to reference Miller JS, Soignier Y, Panoskaltsis-Mortari A, McNearney SA, Yun GH, Fautsch SK, McKenna D, Le C, Defor TE, Burns LJ, et al. Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood. 2005;105(8):3051–7.PubMedCrossRef Miller JS, Soignier Y, Panoskaltsis-Mortari A, McNearney SA, Yun GH, Fautsch SK, McKenna D, Le C, Defor TE, Burns LJ, et al. Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood. 2005;105(8):3051–7.PubMedCrossRef
25.
go back to reference Dong W, Wu X, Ma S, Wang Y, Nalin AP, Zhu Z, Zhang J, Benson DM, He K, Caligiuri MA, et al. The mechanism of Anti-PD-L1 antibody efficacy against PD-L1-Negative tumors identifies NK cells expressing PD-L1 as a Cytolytic Effector. Cancer Discov. 2019;9(10):1422–37.PubMedPubMedCentralCrossRef Dong W, Wu X, Ma S, Wang Y, Nalin AP, Zhu Z, Zhang J, Benson DM, He K, Caligiuri MA, et al. The mechanism of Anti-PD-L1 antibody efficacy against PD-L1-Negative tumors identifies NK cells expressing PD-L1 as a Cytolytic Effector. Cancer Discov. 2019;9(10):1422–37.PubMedPubMedCentralCrossRef
26.
go back to reference Benson DM Jr., Bakan CE, Mishra A, Hofmeister CC, Efebera Y, Becknell B, Baiocchi RA, Zhang J, Yu J, Smith MK, et al. The PD-1/PD-L1 axis modulates the natural killer cell versus multiple myeloma effect: a therapeutic target for CT-011, a novel monoclonal anti-PD-1 antibody. Blood. 2010;116(13):2286–94.PubMedPubMedCentralCrossRef Benson DM Jr., Bakan CE, Mishra A, Hofmeister CC, Efebera Y, Becknell B, Baiocchi RA, Zhang J, Yu J, Smith MK, et al. The PD-1/PD-L1 axis modulates the natural killer cell versus multiple myeloma effect: a therapeutic target for CT-011, a novel monoclonal anti-PD-1 antibody. Blood. 2010;116(13):2286–94.PubMedPubMedCentralCrossRef
27.
go back to reference Cheng H, Xu M, Liu X, Zou X, Zhan N, Xia Y. TWEAK/Fn14 activation induces keratinocyte proliferation under psoriatic inflammation. Exp Dermatol. 2016;25(1):32–7.PubMedCrossRef Cheng H, Xu M, Liu X, Zou X, Zhan N, Xia Y. TWEAK/Fn14 activation induces keratinocyte proliferation under psoriatic inflammation. Exp Dermatol. 2016;25(1):32–7.PubMedCrossRef
28.
go back to reference Jong AY, Wu CH, Li J, Sun J, Fabbri M, Wayne AS, Seeger RC. Large-scale isolation and cytotoxicity of extracellular vesicles derived from activated human natural killer cells. J Extracell Vesicles. 2017;6(1):1294368.PubMedPubMedCentralCrossRef Jong AY, Wu CH, Li J, Sun J, Fabbri M, Wayne AS, Seeger RC. Large-scale isolation and cytotoxicity of extracellular vesicles derived from activated human natural killer cells. J Extracell Vesicles. 2017;6(1):1294368.PubMedPubMedCentralCrossRef
29.
go back to reference Sahm C, Schönfeld K, Wels WS. Expression of IL-15 in NK cells results in rapid enrichment and selective cytotoxicity of gene-modified effectors that carry a tumor-specific antigen receptor. Cancer Immunol Immunotherapy: CII. 2012;61(9):1451–61.PubMedCrossRef Sahm C, Schönfeld K, Wels WS. Expression of IL-15 in NK cells results in rapid enrichment and selective cytotoxicity of gene-modified effectors that carry a tumor-specific antigen receptor. Cancer Immunol Immunotherapy: CII. 2012;61(9):1451–61.PubMedCrossRef
30.
go back to reference Schönfeld K, Sahm C, Zhang C, Naundorf S, Brendel C, Odendahl M, Nowakowska P, Bönig H, Köhl U, Kloess S, et al. Selective inhibition of tumor growth by clonal NK cells expressing an ErbB2/HER2-specific chimeric antigen receptor. Mol Therapy: J Am Soc Gene Therapy. 2015;23(2):330–8.CrossRef Schönfeld K, Sahm C, Zhang C, Naundorf S, Brendel C, Odendahl M, Nowakowska P, Bönig H, Köhl U, Kloess S, et al. Selective inhibition of tumor growth by clonal NK cells expressing an ErbB2/HER2-specific chimeric antigen receptor. Mol Therapy: J Am Soc Gene Therapy. 2015;23(2):330–8.CrossRef
31.
go back to reference Zhang C, Burger MC, Jennewein L, Genßler S, Schönfeld K, Zeiner P, Hattingen E, Harter PN, Mittelbronn M, Tonn T et al. ErbB2/HER2-Specific NK Cells for Targeted Therapy of Glioblastoma. J Natl Cancer Inst 2016, 108(5). Zhang C, Burger MC, Jennewein L, Genßler S, Schönfeld K, Zeiner P, Hattingen E, Harter PN, Mittelbronn M, Tonn T et al. ErbB2/HER2-Specific NK Cells for Targeted Therapy of Glioblastoma. J Natl Cancer Inst 2016, 108(5).
32.
go back to reference Zhu L, Oh JM, Gangadaran P, Kalimuthu S, Baek SH, Jeong SY, Lee SW, Lee J, Ahn BC. Targeting and therapy of Glioblastoma in a mouse model using Exosomes Derived from Natural Killer cells. Front Immunol. 2018;9:824.PubMedPubMedCentralCrossRef Zhu L, Oh JM, Gangadaran P, Kalimuthu S, Baek SH, Jeong SY, Lee SW, Lee J, Ahn BC. Targeting and therapy of Glioblastoma in a mouse model using Exosomes Derived from Natural Killer cells. Front Immunol. 2018;9:824.PubMedPubMedCentralCrossRef
33.
go back to reference Groh V, Rhinehart R, Secrist H, Bauer S, Grabstein KH, Spies T. Broad tumor-associated expression and recognition by tumor-derived gamma delta T cells of MICA and MICB. Proc Natl Acad Sci USA. 1999;96(12):6879–84.PubMedPubMedCentralCrossRef Groh V, Rhinehart R, Secrist H, Bauer S, Grabstein KH, Spies T. Broad tumor-associated expression and recognition by tumor-derived gamma delta T cells of MICA and MICB. Proc Natl Acad Sci USA. 1999;96(12):6879–84.PubMedPubMedCentralCrossRef
34.
37.
go back to reference Davis ID, Skrumsager BK, Cebon J, Nicholaou T, Barlow JW, Moller NP, Skak K, Lundsgaard D, Frederiksen KS, Thygesen P, et al. An open-label, two-arm, phase I trial of recombinant human interleukin-21 in patients with metastatic melanoma. Clin cancer Research: Official J Am Association Cancer Res. 2007;13(12):3630–6.CrossRef Davis ID, Skrumsager BK, Cebon J, Nicholaou T, Barlow JW, Moller NP, Skak K, Lundsgaard D, Frederiksen KS, Thygesen P, et al. An open-label, two-arm, phase I trial of recombinant human interleukin-21 in patients with metastatic melanoma. Clin cancer Research: Official J Am Association Cancer Res. 2007;13(12):3630–6.CrossRef
38.
go back to reference Ettinger R, Sims GP, Fairhurst AM, Robbins R, da Silva YS, Spolski R, Leonard WJ, Lipsky PE. IL-21 induces differentiation of human naive and memory B cells into antibody-secreting plasma cells. J Immunol (Baltimore Md: 1950). 2005;175(12):7867–79.CrossRef Ettinger R, Sims GP, Fairhurst AM, Robbins R, da Silva YS, Spolski R, Leonard WJ, Lipsky PE. IL-21 induces differentiation of human naive and memory B cells into antibody-secreting plasma cells. J Immunol (Baltimore Md: 1950). 2005;175(12):7867–79.CrossRef
39.
go back to reference Ozaki K, Spolski R, Ettinger R, Kim HP, Wang G, Qi CF, Hwu P, Shaffer DJ, Akilesh S, Roopenian DC, et al. Regulation of B cell differentiation and plasma cell generation by IL-21, a novel inducer of Blimp-1 and Bcl-6. J Immunol (Baltimore Md: 1950). 2004;173(9):5361–71.CrossRef Ozaki K, Spolski R, Ettinger R, Kim HP, Wang G, Qi CF, Hwu P, Shaffer DJ, Akilesh S, Roopenian DC, et al. Regulation of B cell differentiation and plasma cell generation by IL-21, a novel inducer of Blimp-1 and Bcl-6. J Immunol (Baltimore Md: 1950). 2004;173(9):5361–71.CrossRef
40.
go back to reference Ozaki K, Spolski R, Feng CG, Qi CF, Cheng J, Sher A, Morse HC 3rd, Liu C, Schwartzberg PL, Leonard WJ. A critical role for IL-21 in regulating immunoglobulin production. Sci (New York NY). 2002;298(5598):1630–4.CrossRef Ozaki K, Spolski R, Feng CG, Qi CF, Cheng J, Sher A, Morse HC 3rd, Liu C, Schwartzberg PL, Leonard WJ. A critical role for IL-21 in regulating immunoglobulin production. Sci (New York NY). 2002;298(5598):1630–4.CrossRef
41.
go back to reference Suto A, Nakajima H, Hirose K, Suzuki K, Kagami S, Seto Y, Hoshimoto A, Saito Y, Foster DC, Iwamoto I. Interleukin 21 prevents antigen-induced IgE production by inhibiting germ line C(epsilon) transcription of IL-4-stimulated B cells. Blood. 2002;100(13):4565–73.PubMedCrossRef Suto A, Nakajima H, Hirose K, Suzuki K, Kagami S, Seto Y, Hoshimoto A, Saito Y, Foster DC, Iwamoto I. Interleukin 21 prevents antigen-induced IgE production by inhibiting germ line C(epsilon) transcription of IL-4-stimulated B cells. Blood. 2002;100(13):4565–73.PubMedCrossRef
42.
go back to reference Burgess SJ, Marusina AI, Pathmanathan I, Borrego F, Coligan JE. IL-21 down-regulates NKG2D/DAP10 expression on human NK and CD8 + T cells. J Immunol (Baltimore Md: 1950). 2006;176(3):1490–7.CrossRef Burgess SJ, Marusina AI, Pathmanathan I, Borrego F, Coligan JE. IL-21 down-regulates NKG2D/DAP10 expression on human NK and CD8 + T cells. J Immunol (Baltimore Md: 1950). 2006;176(3):1490–7.CrossRef
43.
go back to reference di Carlo E, de Totero D, Piazza T, Fabbi M, Ferrini S. Role of IL-21 in immune-regulation and tumor immunotherapy. Cancer Immunol Immunotherapy: CII. 2007;56(9):1323–34.PubMedCrossRef di Carlo E, de Totero D, Piazza T, Fabbi M, Ferrini S. Role of IL-21 in immune-regulation and tumor immunotherapy. Cancer Immunol Immunotherapy: CII. 2007;56(9):1323–34.PubMedCrossRef
44.
go back to reference Elsaesser H, Sauer K, Brooks DG. IL-21 is required to control chronic viral infection. Sci (New York NY). 2009;324(5934):1569–72.CrossRef Elsaesser H, Sauer K, Brooks DG. IL-21 is required to control chronic viral infection. Sci (New York NY). 2009;324(5934):1569–72.CrossRef
45.
go back to reference Parrish-Novak J, Dillon SR, Nelson A, Hammond A, Sprecher C, Gross JA, Johnston J, Madden K, Xu W, West J, et al. Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function. Nature. 2000;408(6808):57–63.PubMedCrossRef Parrish-Novak J, Dillon SR, Nelson A, Hammond A, Sprecher C, Gross JA, Johnston J, Madden K, Xu W, West J, et al. Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function. Nature. 2000;408(6808):57–63.PubMedCrossRef
46.
47.
go back to reference Li Y, Hermanson DL, Moriarity BS, Kaufman DS. Human iPSC-Derived natural killer cells Engineered with chimeric Antigen receptors enhance anti-tumor activity. Cell Stem Cell. 2018;23(2):181–192e185.PubMedPubMedCentralCrossRef Li Y, Hermanson DL, Moriarity BS, Kaufman DS. Human iPSC-Derived natural killer cells Engineered with chimeric Antigen receptors enhance anti-tumor activity. Cell Stem Cell. 2018;23(2):181–192e185.PubMedPubMedCentralCrossRef
48.
go back to reference Quintarelli C, Sivori S, Caruso S, Carlomagno S, Falco M, Boffa I, Orlando D, Guercio M, Abbaszadeh Z, Sinibaldi M, et al. Efficacy of third-party chimeric antigen receptor modified peripheral blood natural killer cells for adoptive cell therapy of B-cell precursor acute lymphoblastic leukemia. Leukemia. 2020;34(4):1102–15.PubMedCrossRef Quintarelli C, Sivori S, Caruso S, Carlomagno S, Falco M, Boffa I, Orlando D, Guercio M, Abbaszadeh Z, Sinibaldi M, et al. Efficacy of third-party chimeric antigen receptor modified peripheral blood natural killer cells for adoptive cell therapy of B-cell precursor acute lymphoblastic leukemia. Leukemia. 2020;34(4):1102–15.PubMedCrossRef
49.
go back to reference Rezvani K, Rouce R, Liu E, Shpall E. Engineering Natural Killer cells for Cancer Immunotherapy. Mol Therapy: J Am Soc Gene Therapy. 2017;25(8):1769–81.CrossRef Rezvani K, Rouce R, Liu E, Shpall E. Engineering Natural Killer cells for Cancer Immunotherapy. Mol Therapy: J Am Soc Gene Therapy. 2017;25(8):1769–81.CrossRef
51.
go back to reference Tonn T, Schwabe D, Klingemann HG, Becker S, Esser R, Koehl U, Suttorp M, Seifried E, Ottmann OG, Bug G. Treatment of patients with advanced cancer with the natural killer cell line NK-92. Cytotherapy. 2013;15(12):1563–70.PubMedCrossRef Tonn T, Schwabe D, Klingemann HG, Becker S, Esser R, Koehl U, Suttorp M, Seifried E, Ottmann OG, Bug G. Treatment of patients with advanced cancer with the natural killer cell line NK-92. Cytotherapy. 2013;15(12):1563–70.PubMedCrossRef
52.
go back to reference Zhang J, Zheng H, Diao Y. Natural killer cells and current applications of chimeric Antigen receptor-modified NK-92 cells in Tumor Immunotherapy. Int J Mol Sci 2019, 20(2). Zhang J, Zheng H, Diao Y. Natural killer cells and current applications of chimeric Antigen receptor-modified NK-92 cells in Tumor Immunotherapy. Int J Mol Sci 2019, 20(2).
53.
go back to reference Gong Y, Klein Wolterink RGJ, Wang J, Bos GMJ, Germeraad WTV. Chimeric antigen receptor natural killer (CAR-NK) cell design and engineering for cancer therapy. J Hematol Oncol. 2021;14(1):73.PubMedPubMedCentralCrossRef Gong Y, Klein Wolterink RGJ, Wang J, Bos GMJ, Germeraad WTV. Chimeric antigen receptor natural killer (CAR-NK) cell design and engineering for cancer therapy. J Hematol Oncol. 2021;14(1):73.PubMedPubMedCentralCrossRef
54.
go back to reference Liu Q, Xu Y, Mou J, Tang K, Fu X, Li Y, Xing Y, Rao Q, Xing H, Tian Z, et al. Irradiated chimeric antigen receptor engineered NK-92MI cells show effective cytotoxicity against CD19(+) malignancy in a mouse model. Cytotherapy. 2020;22(10):552–62.PubMedCrossRef Liu Q, Xu Y, Mou J, Tang K, Fu X, Li Y, Xing Y, Rao Q, Xing H, Tian Z, et al. Irradiated chimeric antigen receptor engineered NK-92MI cells show effective cytotoxicity against CD19(+) malignancy in a mouse model. Cytotherapy. 2020;22(10):552–62.PubMedCrossRef
56.
go back to reference Prajapati K, Perez C, Rojas LBP, Burke B, Guevara-Patino JA. Functions of NKG2D in CD8(+) T cells: an opportunity for immunotherapy. Cell Mol Immunol. 2018;15(5):470–9.PubMedPubMedCentralCrossRef Prajapati K, Perez C, Rojas LBP, Burke B, Guevara-Patino JA. Functions of NKG2D in CD8(+) T cells: an opportunity for immunotherapy. Cell Mol Immunol. 2018;15(5):470–9.PubMedPubMedCentralCrossRef
Metadata
Title
Co-expression of IL-21-Enhanced NKG2D CAR-NK cell therapy for lung cancer
Authors
Yan Zhang
Cong Zhang
Minghong He
Weipeng Xing
Rui Hou
Haijin Zhang
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2024
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-023-11806-1

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