Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

ACC 2024 Congress

Catch up on all the top stories and latest evidence in cardiology research with our ACC 2024 Congress hub page.
ADVANCED SEARCH
Log in
Top
Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2017

Open Access 01-12-2017 | Review

New development in CAR-T cell therapy

Authors: Zhenguang Wang, Zhiqiang Wu, Yang Liu, Weidong Han

Published in: Journal of Hematology & Oncology | Issue 1/2017

Login to get access

Abstract

Chimeric antigen receptor (CAR)-engineered T cells (CAR-T cells) have yielded unprecedented efficacy in B cell malignancies, most remarkably in anti-CD19 CAR-T cells for B cell acute lymphoblastic leukemia (B-ALL) with up to a 90% complete remission rate. However, tumor antigen escape has emerged as a main challenge for the long-term disease control of this promising immunotherapy in B cell malignancies. In addition, this success has encountered significant hurdles in translation to solid tumors, and the safety of the on-target/off-tumor recognition of normal tissues is one of the main reasons. In this mini-review, we characterize some of the mechanisms for antigen loss relapse and new strategies to address this issue. In addition, we discuss some novel CAR designs that are being considered to enhance the safety of CAR-T cell therapy in solid tumors.
Literature
1.
Eshhar Z. The T-body approach: redirecting T cells with antibody specificity. Handb Exp Pharmacol. 2008;181:329–42.CrossRef
2.
Curran KJ, Pegram HJ, Brentjens RJ. Chimeric antigen receptors for T cell immunotherapy: current understanding and future directions. J Gene Med. 2012;14(6):405–15.CrossRefPubMedPubMedCentral
3.
Dai H, Wang Y, Lu X, Han W. Chimeric antigen receptors modified T-cells for cancer therapy. J Natl Cancer Inst. 2016;108(7):djv439.
4.
Eshhar Z, Waks T, Gross G, Schindler DG. Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the gamma or zeta subunits of the immunoglobulin and T-cell receptors. Proc Natl Acad Sci U S A. 1993;90(2):720–4.CrossRefPubMedPubMedCentral
5.
Turtle CJ, Hanafi LA, Berger C, Gooley TA, Cherian S, Hudecek M, Sommermeyer D, Melville K, Pender B, Budiarto TM, et al. CD19 CAR-T cells of defined CD4+:CD8+ composition in adult B cell ALL patients. J Clin Invest. 2016;126(6):2123–38.CrossRefPubMedPubMedCentral
6.
Lee DW, Kochenderfer JN, Stetler-Stevenson M, Cui YK, Delbrook C, Feldman SA, Fry TJ, Orentas R, Sabatino M, Shah NN, et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet (London, England). 2015;385(9967):517–28.CrossRef
7.
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.CrossRefPubMedPubMedCentral
8.
Davila ML, Riviere I, Wang X, Bartido S, Park J, Curran K, Chung SS, Stefanski J, Borquez-Ojeda O, Olszewska M, et al. Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci Transl Med. 2014;6(224):224ra225.CrossRef
9.
Turtle CJ, Hanafi LA, Berger C, Hudecek M, Pender B, Robinson E, Hawkins R, Chaney C, Cherian S, Chen X, et al. Immunotherapy of non-Hodgkin’s lymphoma with a defined ratio of CD8+ and CD4+ CD19-specific chimeric antigen receptor-modified T cells. Sci Transl Med. 2016;8(355):355ra116.CrossRefPubMed
10.
Kochenderfer JN, Dudley ME, Kassim SH, Somerville RP, Carpenter RO, Stetler-Stevenson M, Yang JC, Phan GQ, Hughes MS, Sherry RM, et al. Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor. J Clin Oncol. 2015;33(6):540–9.CrossRefPubMed
11.
Kalos M, Levine BL, Porter DL, Katz S, Grupp SA, Bagg A, June CH. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med. 2011;3(95):95ra73.CrossRefPubMedPubMedCentral
12.
Grupp SA, Maude SL, Shaw PA, Aplenc R, Barrett DM, Callahan C, Lacey SF, Levine BL, Melenhorst JJ, Motley L, et al. Durable remissions in children with relapsed/refractory ALL treated with T cells engineered with a CD19-targeted chimeric antigen receptor (CTL019). Blood. 2015;126(23):681.
13.
Cai B, Guo M, Wang Y, Zhang Y, Yang J, Guo Y, Dai H, Yu C, Sun Q, Qiao J, et al. Co-infusion of haplo-identical CD19-chimeric antigen receptor T cells and stem cells achieved full donor engraftment in refractory acute lymphoblastic leukemia. J Hematol Oncol. 2016;9(1):131.CrossRefPubMedPubMedCentral
14.
Zhang W-y, Wang Y, Guo Y-l, Dai H, Yang Q-m, Zhang Y-j, Zhang Y, Chen M-x, Wang C-m, Feng K-c, et al. Treatment of CD20-directed chimeric antigen receptor-modified T cells in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an early phase IIa trial report. Signal Transduction TargetTher. 2016;1:16002.CrossRef
15.
Wang CM, Wu ZQ, Wang Y, Guo YL, Dai HR, Wang XH, Li X, Zhang YJ, Zhang WY, Chen MX, et al. Autologous T Cells expressing CD30 chimeric antigen receptors for relapsed or refractory Hodgkin lymphoma: an open-label phase I trial. Clin Cancer Res. 2016. doi:10.​1158/​1078-0432.​CCR-16-1365.
16.
Feng K, Guo Y, Dai H, Wang Y, Li X, Jia H, Han W. Chimeric antigen receptor-modified T cells for the immunotherapy of patients with EGFR-expressing advanced relapsed/refractory non-small cell lung cancer. Sci China Life Sci. 2016;59(5):468–79.CrossRefPubMed
17.
Beatty GL, Haas AR, Maus MV, Torigian DA, Soulen MC, Plesa G, Chew A, Zhao Y, Levine BL, Albelda SM, et al. Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce anti-tumor activity in solid malignancies. Cancer Immunol Res. 2014;2(2):112–20.CrossRefPubMed
18.
Maus MV, Haas AR, Beatty GL, Albelda SM, Levine BL, Liu X, Zhao Y, Kalos M, June CH. T cells expressing chimeric antigen receptors can cause anaphylaxis in humans. Cancer Immunol Res. 2013;1(1):26–31.CrossRefPubMedCentral
19.
O’Rourke DM, Nasrallah M, Morrissette JJ, Melenhorst JJ, Lacey SF, Mansfield K, Martinez-Lage M, Desai AS, Brem S, Maloney E, et al. Pilot study of T cells redirected to EGFRvIII with a chimeric antigen receptor in patients with EGFRvIII+ glioblastoma. ASCO Meeting Abstracts. 2016;34(15_suppl):2067.
20.
Morgan RA, Yang JC, Kitano M, Dudley ME, Laurencot CM, Rosenberg SA. Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol Ther. 2010;18(4):843–51.CrossRefPubMedPubMedCentral
21.
Ahmed N, Brawley VS, Hegde M, Robertson C, Ghazi A, Gerken C, Liu E, Dakhova O, Ashoori A, Corder A, et al. Human epidermal growth factor receptor 2 (HER2)—specific chimeric antigen receptor-modified T cells for the immunotherapy of HER2-positive sarcoma. J Clin Oncol. 2015;33(15):1688–96.CrossRefPubMedPubMedCentral
22.
Katz SC, Burga RA, McCormack E, Wang LJ, Mooring W, Point GR, Khare PD, Thorn M, Ma Q, Stainken BF, et al. Phase I hepatic immunotherapy for metastases study of intra-arterial chimeric antigen receptor-modified T-cell therapy for CEA+ liver metastases. Clin Cancer Res. 2015;21(14):3149–59.CrossRefPubMedPubMedCentral
23.
Slovin SF, Wang X, Borquez-Ojeda O, Stefanski J, Olszewska M, Taylor C, Bartido S, Scher HI, Sadelain M, Riviere I. Targeting castration resistant prostate cancer (CRPC) with autologous PSMA-directed CAR+ T cells. ASCO Meeting Abstracts. 2012;30(15_suppl):TPS4700.
24.
Maude SL, Teachey DT, Rheingold SR, Shaw PA, Aplenc R, Barrett DM, Barker CS, Callahan C, Frey NV, Nazimuddin F, et al. Sustained remissions with CD19-specific chimeric antigen receptor (CAR)-modified T cells in children with relapsed/refractory ALL. ASCO Meeting Abstracts. 2016;34(15_suppl):3011.
25.
Lee DW, Stetler-Stevenson M, Yuan CM, Fry TJ, Shah NN, Delbrook C, Yates B, Zhang H, Zhang L, Kochenderfer JN, et al. Safety and response of incorporating CD19 chimeric antigen receptor T cell therapy in typical salvage regimens for children and young adults with acute lymphoblastic leukemia. Blood. 2015;126(23):684.
26.
Park JH, Riviere I, Wang X, Bernal Y, Purdon T, Halton E, Curran KJ, Sauter CS, Sadelain M, Brentjens RJ. Efficacy and safety of CD19-targeted 19-28z CAR modified T cells in adult patients with relapsed or refractory B-ALL. J Clin Oncol. 2015;33(15_suppl):7010.
27.
Pegram HJ, Smith EL, Rafiq S, Brentjens RJ. CAR therapy for hematological cancers: can success seen in the treatment of B-cell acute lymphoblastic leukemia be applied to other hematological malignancies? Immunotherapy. 2015;7(5):545–61.CrossRefPubMedPubMedCentral
28.
Evans AG, Rothberg PG, Burack WR, Huntington SF, Porter DL, Friedberg JW, Liesveld JL. Evolution to plasmablastic lymphoma evades CD19-directed chimeric antigen receptor T cells. Br J Haematol. 2015. doi:10.​1111/​bjh.​13562.PubMedCentral
29.
Yu H, Sotillo E, Harrington C, Wertheim G, Paessler M, Maude SL, Rheingold SR, Grupp SA, Thomas-Tikhonenko A, Pillai V. Repeated loss of target surface antigen after immunotherapy in primary mediastinal large B cell lymphoma. Am J Hematol. 2017;92(1):E11–3.CrossRefPubMed
30.
Yannakou CK, Came N, Bajel AR, Juneja S. CD19 negative relapse in B-ALL treated with blinatumomab therapy: avoiding the trap. Blood. 2015;126:4983.
31.
32.
Kohnke T, Krupka C, Tischer J, Knosel T, Subklewe M. Increase of PD-L1 expressing B-precursor ALL cells in a patient resistant to the CD19/CD3-bispecific T cell engager antibody blinatumomab. J Hematol Oncol. 2015;8:111.CrossRefPubMedPubMedCentral
33.
Fan D, Li W, Yang Y, Zhang X, Zhang Q, Yan Y, Yang M, Wang J, Xiong D. Redirection of CD4+ and CD8+ T lymphocytes via an anti-CD3 × anti-CD19 bi-specific antibody combined with cytosine arabinoside and the efficient lysis of patient-derived B-ALL cells. J Hematol Oncol. 2015;8:108.CrossRefPubMedPubMedCentral
34.
Linder K, Gandhiraj D, Hanmantgad M, Seiter K, Liu D. Complete remission after single agent blinatumomab in a patient with pre-B acute lymphoid leukemia relapsed and refractory to three prior regimens: hyperCVAD, high dose cytarabine mitoxantrone and CLAG. Exp Hematol Oncol. 2015;5:20.CrossRefPubMed
35.
Wu J, Fu J, Zhang M, Liu D. Blinatumomab: a bispecific T cell engager (BiTE) antibody against CD19/CD3 for refractory acute lymphoid leukemia. J Hematol Oncol. 2015;8:104.CrossRefPubMedPubMedCentral
36.
37.
Wang QS, Wang Y, Lv HY, Han QW, Fan H, Guo B, Wang LL, Han WD. Treatment of CD33-directed chimeric antigen receptor-modified T cells in one patient with relapsed and refractory acute myeloid leukemia. Mol Ther. 2015;23(1):184–91.CrossRefPubMed
38.
Hegde M, Corder A, Chow KK, Mukherjee M, Ashoori A, Kew Y, Zhang YJ, Baskin DS, Merchant FA, Brawley VS, et al. Combinational targeting offsets antigen escape and enhances effector functions of adoptively transferred T cells in glioblastoma. Mol Ther. 2013;21(11):2087–101.CrossRefPubMedCentral
39.
Sotillo E, Barrett DM, Black KL, Bagashev A, Oldridge D, Wu G, Sussman R, Lanauze C, Ruella M, Gazzara MR, et al. Convergence of acquired mutations and alternative splicing of CD19 enables resistance to CART-19 immunotherapy. Cancer Discov. 2015;5(12):1282–95.CrossRefPubMedPubMedCentral
40.
Perna F, Sadelain M. Myeloid leukemia switch as immune escape from CD19 chimeric antigen receptor (CAR) therapy. Transl Cancer Res. 2016;5(S2):S221–5.CrossRef
41.
Gardner R, Wu D, Cherian S, Fang M, Hanafi LA, Finney O, Smithers H, Jensen MC, Riddell SR, Maloney DG, et al. Acquisition of a CD19 negative myeloid phenotype allows immune escape of MLL-rearranged B-ALL from CD19 CAR-T cell therapy. Blood. 2016;127(20):2406–10.CrossRefPubMed
42.
Jacoby E, Nguyen SM, Fountaine TJ, Welp K, Gryder B, Qin H, Yang Y, Chien CD, Seif AE, Lei H, et al. CD19 CAR immune pressure induces B-precursor acute lymphoblastic leukaemia lineage switch exposing inherent leukaemic plasticity. Nat Commun. 2016;7:12320.CrossRefPubMedPubMedCentral
43.
Ruella M, Barrett DM, Kenderian SS, Shestova O, Hofmann TJ, Perazzelli J, Klichinsky M, Aikawa V, Nazimuddin F, Kozlowski M, et al. Dual CD19 and CD123 targeting prevents antigen-loss relapses after CD19-directed immunotherapies. J Clin Invest. 2016;126(10):3814–26.CrossRefPubMedPubMedCentral
44.
Zah E, Lin MY, Silva-Benedict A, Jensen MC, Chen YY. T cells expressing CD19/CD20 bi-specific chimeric antigen receptors prevent antigen escape by malignant B cells. Cancer Immunol Res. 2016. doi:10.​1158/​2326-6066.​CIR-15-0231.
45.
Hegde M, Mukherjee M, Grada Z, Pignata A, Landi D, Navai SA, Wakefield A, Fousek K, Bielamowicz K, Chow KK, et al. Tandem CAR T cells targeting HER2 and IL13Ralpha2 mitigate tumor antigen escape. J Clin Invest. 2016;126(8):3036–52.CrossRefPubMedPubMedCentral
46.
Grada Z, Hegde M, Byrd T, Shaffer DR, Ghazi A, Brawley VS, Corder A, Schonfeld K, Koch J, Dotti G, et al. TanCAR: a novel bispecific chimeric antigen receptor for cancer immunotherapy. Mol Ther Nucleic Acids. 2013;2:e105.CrossRefPubMedPubMedCentral
47.
48.
Fan D, Li Z, Zhang X, Yang Y, Yuan X, Zhang X, Yang M, Zhang Y, Xiong D. AntiCD3Fv fused to human interleukin-3 deletion variant redirected T cells against human acute myeloid leukemic stem cells. J Hematol Oncol. 2015;8:18.CrossRefPubMedPubMedCentral
49.
Feng KC, Guo YL, Liu Y, Dai HR, Wang Y, Lv HY, Huang JH, Yang QM, Han WD. Cocktail treatment with EGFR-specific and CD133-specific chimeric antigen receptor-modified T cells in a patient with advanced cholangiocarcinoma. J Hematol Oncol. 2017;10(1):4.CrossRefPubMedPubMedCentral
50.
Ning N, Pan Q, Zheng F, Teitz-Tennenbaum S, Egenti M, Yet J, Li M, Ginestier C, Wicha MS, Moyer JS, et al. Cancer stem cell vaccination confers significant antitumor immunity. Cancer Res. 2012;72(7):1853–64.CrossRefPubMedPubMedCentral
51.
Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414(6859):105–11.CrossRefPubMed
52.
Hermann PC, Bhaskar S, Cioffi M, Heeschen C. Cancer stem cells in solid tumors. Semin Cancer Biol. 2010;20(2):77–84.CrossRefPubMed
53.
Jackson HJ, Brentjens RJ. Overcoming antigen escape with CAR T-cell therapy. Cancer Discov. 2015;5(12):1238–40.CrossRefPubMed
54.
Ribas A, Timmerman JM, Butterfield LH, Economou JS. Determinant spreading and tumor responses after peptide-based cancer immunotherapy. Trends Immunol. 2003;24(2):58–61.CrossRefPubMed
55.
Park JH, Riviere I, Wang X, Bernal Y, Purdon T, Halton E, Wang Y, Curran KJ, Sauter CS, Sadelain M, et al. Implications of minimal residual disease negative complete remission (MRD-CR) and allogeneic stem cell transplant on safety and clinical outcome of CD19-targeted 19-28z CAR modified T cells in adult patients with relapsed, refractory B-cell ALL. Blood. 2015;126(23):682.
56.
Li G, Wong AJ. EGF receptor variant III as a target antigen for tumor immunotherapy. Expert Rev Vaccines. 2008;7(7):977–85.CrossRefPubMed
57.
Posey Jr AD, Schwab RD, Boesteanu AC, Steentoft C, Mandel U, Engels B, Stone JD, Madsen TD, Schreiber K, Haines KM, et al. Engineered CAR T cells targeting the cancer-associated Tn-glycoform of the membrane mucin MUC1 control adenocarcinoma. Immunity. 2016;44(6):1444–54.CrossRefPubMed
58.
Noy R, Eppel M, Haus-Cohen M, Klechevsky E, Mekler O, Michaeli Y, Denkberg G, Reiter Y. T-cell receptor-like antibodies: novel reagents for clinical cancer immunology and immunotherapy. Expert Rev Anticancer Ther. 2005;5(3):523–36.CrossRefPubMed
59.
Dahan R, Reiter Y. T-cell-receptor-like antibodies—generation, function and applications. Expert Rev Mol Med. 2012;14:e6.CrossRefPubMed
60.
Liu H, Xu Y, Xiang J, Long L, Green S, Yang Z, Zimdahl B, Lu J, Cheng N, Horan LH, et al. Targeting alpha-fetoprotein (AFP)-MHC complex with CAR T cell therapy for liver cancer. Clin Cancer Res. 2016. doi:10.​1158/​1078-0432.​CCR-16-1203.
61.
Ma Q, Garber HR, Lu S, He H, Tallis E, Ding X, Sergeeva A, Wood MS, Dotti G, Salvado B, et al. A novel TCR-like CAR with specificity for PR1/HLA-A2 effectively targets myeloid leukemia in vitro when expressed in human adult peripheral blood and cord blood T cells. Cytotherapy. 2016;18(8):985–94.CrossRefPubMed
62.
Zhang G, Wang L, Cui H, Wang X, Zhang G, Ma J, Han H, He W, Wang W, Zhao Y, et al. Anti-melanoma activity of T cells redirected with a TCR-like chimeric antigen receptor. Sci Rep. 2014;4:3571.PubMedPubMedCentral
63.
Gross G, Eshhar Z. Therapeutic potential of T cell chimeric antigen receptors (CARs) in cancer treatment: counteracting off-tumor toxicities for safe CAR T cell therapy. Annu Rev Pharmacol Toxicol. 2016;56:59–83.CrossRefPubMed
64.
Wilkie S, van Schalkwyk MC, Hobbs S, Davies DM, van der Stegen SJ, Pereira AC, Burbridge SE, Box C, Eccles SA, Maher J. Dual targeting of ErbB2 and MUC1 in breast cancer using chimeric antigen receptors engineered to provide complementary signaling. J Clin Immunol. 2012;32(5):1059–70.CrossRefPubMed
65.
Kloss CC, Condomines M, Cartellieri M, Bachmann M, Sadelain M. Combinatorial antigen recognition with balanced signaling promotes selective tumor eradication by engineered T cells. Nat Biotechnol. 2013;31(1):71–5.CrossRefPubMed
66.
Hanada K, Restifo NP. Double or nothing on cancer immunotherapy. Nat Biotechnol. 2013;31(1):33–4.CrossRefPubMed
67.
Morsut L, Roybal KT, Xiong X, Gordley RM, Coyle SM, Thomson M, Lim WA. Engineering customized cell sensing and response behaviors using synthetic notch receptors. Cell. 2016;164(4):780–91.CrossRefPubMedPubMedCentral
68.
Roybal KT, Rupp LJ, Morsut L, Walker WJ, McNally KA, Park JS, Lim WA. Precision tumor recognition by T cells with combinatorial antigen-sensing circuits. Cell. 2016;164(4):770–9.CrossRefPubMedPubMedCentral
69.
70.
Fedorov VD, Themeli M, Sadelain M. PD-1- and CTLA-4-based inhibitory chimeric antigen receptors (iCARs) divert off-target immunotherapy responses. Sci Transl Med. 2013;5(215):215ra172.CrossRefPubMedPubMedCentral
71.
Tan MP, Gerry AB, Brewer JE, Melchiori L, Bridgeman JS, Bennett AD, Pumphrey NJ, Jakobsen BK, Price DA, Ladell K, et al. T cell receptor binding affinity governs the functional profile of cancer-specific CD8+ T cells. Clin Exp Immunol. 2015;180(2):255–70.CrossRefPubMedPubMedCentral
72.
Zhong S, Malecek K, Johnson LA, Yu Z, Vega-Saenz de Miera E, Darvishian F, McGary K, Huang K, Boyer J, Corse E, et al. T-cell receptor affinity and avidity defines antitumor response and autoimmunity in T-cell immunotherapy. Proc Natl Acad Sci U S A. 2013;110(17):6973–8.CrossRefPubMedPubMedCentral
73.
Chmielewski M, Hombach A, Heuser C, Adams GP, Abken H. T cell activation by antibody-like immunoreceptors: increase in affinity of the single-chain fragment domain above threshold does not increase T cell activation against antigen-positive target cells but decreases selectivity. J Immunol. 2004;173(12):7647–53.CrossRefPubMed
74.
Caruso HG, Hurton LV, Najjar A, Rushworth D, Ang S, Olivares S, Mi T, Switzer K, Singh H, Huls H, et al. Tuning sensitivity of CAR to EGFR density limits recognition of normal tissue while maintaining potent antitumor activity. Cancer Res. 2015;75(17):3505–18.CrossRefPubMedPubMedCentral
75.
Liu X, Jiang S, Fang C, Yang S, Olalere D, Pequignot EC, Cogdill AP, Li N, Ramones M, Granda B, et al. Affinity-tuned ErbB2 or EGFR chimeric antigen receptor T cells exhibit an increased therapeutic index against tumors in mice. Cancer Res. 2015;75(17):3596–607.CrossRefPubMedPubMedCentral
76.
Harris DT, Kranz DM. Adoptive T cell therapies: a comparison of T cell receptors and chimeric antigen receptors. Trends Pharmacol Sci. 2016;37(3):220–30.CrossRefPubMed
77.
Erster O, Thomas JM, Hamzah J, Jabaiah AM, Getz JA, Schoep TD, Hall SS, Ruoslahti E, Daugherty PS. Site-specific targeting of antibody activity in vivo mediated by disease-associated proteases. J Control Release. 2012;161(3):804–12.CrossRefPubMedPubMedCentral
78.
Desnoyers LR, Vasiljeva O, Richardson JH, Yang A, Menendez EE, Liang TW, Wong C, Bessette PH, Kamath K, Moore SJ, et al. Tumor-specific activation of an EGFR-targeting probody enhances therapeutic index. Sci Transl Med. 2013;5(207):207ra144.CrossRefPubMed
79.
Klebanoff CA, Rosenberg SA, Restifo NP. Prospects for gene-engineered T cell immunotherapy for solid cancers. Nat Med. 2016;22(1):26–36.CrossRefPubMed
80.
Gill S, June CH. Going viral: chimeric antigen receptor T-cell therapy for hematological malignancies. Immunol Rev. 2015;263(1):68–89.CrossRefPubMed
81.
Zhao Y, Moon E, Carpenito C, Paulos CM, Liu X, Brennan AL, Chew A, Carroll RG, Scholler J, Levine BL, et al. Multiple injections of electroporated autologous T cells expressing a chimeric antigen receptor mediate regression of human disseminated tumor. Cancer Res. 2010;70(22):9053–61.CrossRefPubMedPubMedCentral
82.
Barrett DM, Zhao Y, Liu X, Jiang S, Carpenito C, Kalos M, Carroll RG, June CH, Grupp SA. Treatment of advanced leukemia in mice with mRNA engineered T cells. Hum Gene Ther. 2011;22(12):1575–86.CrossRefPubMedPubMedCentral
83.
Tanyi JL, Haas AR, Beatty GL, Morgan MA, Stashwick CJ, O’Hara MH, Porter DL, Maus MV, Levine BL, Lacey SF, et al. Abstract CT105: Safety and feasibility of chimeric antigen receptor modified T cells directed against mesothelin (CART-meso) in patients with mesothelin expressing cancers. Cancer Res. 2015;75(15 Supplement):CT105.CrossRef
84.
Juillerat A, Marechal A, Filhol JM, Valton J, Duclert A, Poirot L, Duchateau P. Design of chimeric antigen receptors with integrated controllable transient functions. Sci Rep. 2016;6:18950.CrossRefPubMedPubMedCentral
85.
Wu CY, Roybal KT, Puchner EM, Onuffer J, Lim WA. Remote control of therapeutic T cells through a small molecule-gated chimeric receptor. Science. 2015;350(6258):aab4077.CrossRefPubMedPubMedCentral
86.
Cao Y, Rodgers DT, Du J, Ahmad I, Hampton EN, Ma JS, Mazagova M, Choi SH, Yun HY, Xiao H, et al. Design of switchable chimeric antigen receptor T cells targeting breast cancer. Angew Chem Int Ed Engl. 2016;55(26):7520–4.CrossRefPubMed
87.
Kim MS, Ma JS, Yun H, Cao Y, Kim JY, Chi V, Wang D, Woods A, Sherwood L, Caballero D, et al. Redirection of genetically engineered CAR-T cells using bifunctional small molecules. J Am Chem Soc. 2015;137(8):2832–5.CrossRefPubMed
88.
Ma JS, Kim JY, Kazane SA, Choi SH, Yun HY, Kim MS, Rodgers DT, Pugh HM, Singer O, Sun SB, et al. Versatile strategy for controlling the specificity and activity of engineered T cells. Proc Natl Acad Sci U S A. 2016;113(4):E450–8.CrossRefPubMedPubMedCentral
89.
Liu K, Liu X, Peng Z, Sun H, Zhang M, Zhang J, Liu S, Hao L, Lu G, Zheng K, et al. Retargeted human avidin-CAR T cells for adoptive immunotherapy of EGFRvIII expressing gliomas and their evaluation via optical imaging. Oncotarget. 2015;6(27):23735–47.CrossRefPubMedPubMedCentral
90.
Rodgers DT, Mazagova M, Hampton EN, Cao Y, Ramadoss NS, Hardy IR, Schulman A, Du J, Wang F, Singer O, et al. Switch-mediated activation and retargeting of CAR-T cells for B-cell malignancies. Proc Natl Acad Sci U S A. 2016;113(4):E459–68.CrossRefPubMedPubMedCentral
91.
92.
Di Stasi A, Tey SK, Dotti G, Fujita Y, Kennedy-Nasser A, Martinez C, Straathof K, Liu E, Durett AG, Grilley B, et al. Inducible apoptosis as a safety switch for adoptive cell therapy. N Engl J Med. 2011;365(18):1673–83.CrossRefPubMedPubMedCentral
93.
94.
Wang X, Chang WC, Wong CW, Colcher D, Sherman M, Ostberg JR, Forman SJ, Riddell SR, Jensen MC. A transgene-encoded cell surface polypeptide for selection, in vivo tracking, and ablation of engineered cells. Blood. 2011;118(5):1255–63.CrossRefPubMedPubMedCentral
Metadata
Title
New development in CAR-T cell therapy
Authors
Zhenguang Wang
Zhiqiang Wu
Yang Liu
Weidong Han
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2017
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-017-0423-1

Other articles of this Issue 1/2017

Journal of Hematology & Oncology 1/2017 Go to the issue

Research

Antitumor activity of miR-34a in peritoneal mesothelioma relies on c-MET and AXL inhibition: persistent activation of ERK and AKT signaling as a possible cytoprotective mechanism

Research

Tumor-recruited M2 macrophages promote gastric and breast cancer metastasis via M2 macrophage-secreted CHI3L1 protein

Letter to the Editor

Different clinical characteristics and treatment strategies for patients with localized sinonasal diffuse large B cell lymphoma and extranodal NK/T cell lymphoma

Review

Anti-claudin 18.2 antibody as new targeted therapy for advanced gastric cancer

Research

The dynamics of RUNX1-RUNX1T1 transcript levels after allogeneic hematopoietic stem cell transplantation predict relapse in patients with t(8;21) acute myeloid leukemia

Review

Extracellular vesicles-mediated noncoding RNAs transfer in cancer
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

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
Image Credits