CAR models: Next-generation CAR modifications for enhanced T-cell function

Molecular Therapy Oncolytics

Volumn 3, Issue , 2016, Pages 16014-

  Abate Daga, Daniel ^a,b   Davila, Marco L ^a,b  

^a H LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE   (United States)

^b UNIVERSITY OF SOUTH FLORIDA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHIMERIC ANTIGEN RECEPTOR; SINGLE CHAIN FRAGMENT VARIABLE ANTIBODY;

ADOPTIVE IMMUNOTHERAPY; ANTIGEN BINDING; ANTIGEN SPECIFICITY; ARTICLE; CANCER IMMUNOTHERAPY; CLINICAL TRIAL (TOPIC); DNA MODIFICATION; DRUG EFFICACY; GENE EXPRESSION; HINGE REGION; HUMAN; INTRACELLULAR SIGNALING; LYMPHOCYTE FUNCTION; MOLECULARLY TARGETED THERAPY; NONHUMAN; PRIORITY JOURNAL; PROTEIN STRUCTURE; SIGNAL TRANSDUCTION; SPACER DOMAIN; T LYMPHOCYTE;

EID: 84991518662     PISSN: None     EISSN: 23727705     Source Type: Journal    
DOI: 10.1038/mto.2016.14     Document Type: Review

References (72)

1. Sadelain, M, Riviere, I and Brentjens, R (2003). Targeting tumours with genetically enhanced T lymphocytes. Nat Rev Cancer 3: 35-45.
2. Abraham, RT and Weiss, A (2004). Jurkat T cells and development of the T-cell receptor signalling paradigm. Nat Rev Immunol 4: 301-308.
3. Irving, BA and Weiss, A (1991). The cytoplasmic domain of the T cell receptor zeta chain is sufficient to couple to receptor-associated signal transduction pathways. Cell 64: 891-901.
4. Restifo, NP, Dudley, ME and Rosenberg, SA (2012). Adoptive immunotherapy for cancer: harnessing the T cell response. Nat Rev Immunol 12: 269-281.
5. Stevanovi, S, Draper, LM, Langhan, MM, Campbell, TE, Kwong, ML, Wunderlich, JR et al. (2015). Complete regression of metastatic cervical cancer after treatment with human papillomavirus-targeted tumor-infiltrating T cells. J Clin Oncol 33: 1543-1550.
6. Dudley, ME, Yang, JC, Sherry, R, Hughes, MS, Royal, R, Kammula, U et al. (2008). Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens. J Clin Oncol 26: 5233-5239.
7. Klapper, JA, Thomasian, AA, Smith, DM, Gorgas, GC, Wunderlich, JR, Smith, FO et al. (2009). Single-pass, closed-system rapid expansion of lymphocyte cultures for adoptive cell therapy. J Immunol Methods 345: 90-99.
8. Hollyman, D, Stefanski, J, Przybylowski, M, Bartido, S, Borquez-Ojeda, O, Taylor, C et al. (2009). Manufacturing validation of biologically functional T cells targeted to CD19 antigen for autologous adoptive cell therapy. J Immunother 32: 169-180.
9. Kochenderfer, JN, Feldman, SA, Zhao, Y, Xu, H, Black, MA, Morgan, RA et al. (2009). Construction and preclinical evaluation of an anti-CD19 chimeric antigen receptor. J Immunother 32: 689-702.
10. Davila, ML, Sauter, C and Brentjens, R (2015). CD19-targeted T cells for hematologic malignancies: clinical experience to date. Cancer J 21: 470-474.
11. Brocker, T and Karjalainen, K (1995). Signals through T cell receptor-zeta chain alone are insufficient to prime resting T lymphocytes. J Exp Med 181: 1653-1659.
12. Rossjohn, J, Gras, S, Miles, JJ, Turner, SJ, Godfrey, DI and McCluskey, J (2015). T cell antigen receptor recognition of antigen-presenting molecules. Annu Rev Immunol 33: 169-200.
13. Sharpe, AH and Freeman, GJ (2002). The B7-CD28 superfamily. Nat Rev Immunol 2: 116-126.
14. Maher, J, Brentjens, RJ, Gunset, G, Riviere, I and Sadelain, M (2002). Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCRzeta /CD28 receptor. Nat Biotechnol 20: 70-75.
15. Hombach, A, Wieczarkowiecz, A, Marquardt, T, Heuser, C, Usai, L, Pohl, C et al. (2001). Tumor-specific T cell activation by recombinant immunoreceptors: CD3 zeta signaling and CD28 costimulation are simultaneously required for efficient IL-2 secretion and can be integrated into one combined CD28/CD3 zeta signaling receptor molecule. J Immunol 167: 6123-6131.
16. Finney, HM, Lawson, AD, Bebbington, CR and Weir, AN (1998). Chimeric receptors providing both primary and costimulatory signaling in T cells from a single gene product. J Immunol 161: 2791-2797.
17. Imai, C, Mihara, K, Andreansky, M, Nicholson, IC, Pui, CH, Geiger, TL et al. (2004). Chimeric receptors with 4-1BB signaling capacity provoke potent cytotoxicity against acute lymphoblastic leukemia. Leukemia 18: 676-684.
18. Song, DG, Ye, Q, Poussin, M, Harms, GM, Figini, M and Powell, DJ Jr (2012). CD27 costimulation augments the survival and antitumor activity of redirected human T cells in vivo. Blood 119: 696-706.
19. Hombach, AA and Abken, H (2013). Of chimeric antigen receptors and antibodies: OX40 and 41BB costimulation sharpen up T cell-based immunotherapy of cancer. Immunotherapy 5: 677-681.
20. Davila, ML, Riviere, I, Wang, X, Bartido, S, Park, J, Curran, K et al. (2014). Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci Transl Med 6: 224ra25.
21. Maude, SL, Frey, N, Shaw, PA, Aplenc, R, Barrett, DM, Bunin, NJ et al. (2014). Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med 371: 1507-1517.
22. Lee, DW, Kochenderfer, JN, Stetler-Stevenson, M, Cui, YK, Delbrook, C, Feldman, SA et al. (2015). T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: A phase 1 dose-escalation trial. Lancet 385: 517-528.
23. Jensen, MC, Popplewell, L, Cooper, LJ, DiGiusto, D, Kalos, M, Ostberg, JR et al. (2010). Antitransgene rejection responses contribute to attenuated persistence of adoptively transferred CD20/CD19-specific chimeric antigen receptor redirected T cells in humans. Biol Blood Marrow Transplant 16: 1245-1256.
24. Maus, MV, Haas, AR, Beatty, GL, Albelda, SM, Levine, BL, Liu, X et al. (2013). T cells expressing chimeric antigen receptors can cause anaphylaxis in humans. Cancer Immunol Res 1: 26-31.
25. Kalos, M, Levine, BL, Porter, DL, Katz, S, Grupp, SA, Bagg, A et al. (2011). T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med 3: 95ra73.
26. Kochenderfer, JN, Dudley, ME, Feldman, SA, Wilson, WH, Spaner, DE, Maric, I et al. (2012). B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells. Blood 119: 2709-2720.
27. Morgan, RA, Yang, JC, Kitano, M, Dudley, ME, Laurencot, CM and Rosenberg, SA (2010). Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol Ther 18: 843-851.
28. Liu, X, Jiang, S, Fang, C, Yang, S, Olalere, D, Pequignot, EC et al. (2015). Affinity-tuned ErbB2 or EGFR chimeric antigen receptor T cells exhibit an increased therapeutic index against tumors in mice. Cancer Res 75: 3596-3607.
29. Caruso, HG, Hurton, LV, Najjar, A, Rushworth, D, Ang, S, Olivares, S et al. (2015). Tuning sensitivity of CAR to EGFR density limits recognition of normal tissue while maintaining potent antitumor activity. Cancer Res 75: 3505-3518.
30. Kloss, CC, Condomines, M, Cartellieri, M, Bachmann, M and Sadelain, M (2013). Combinatorial antigen recognition with balanced signaling promotes selective tumor eradication by engineered T cells. Nat Biotechnol 31: 71-75.
31. Grada, Z, Hegde, M, Byrd, T, Shaffer, DR, Ghazi, A, Brawley, VS et al. (2013). TanCAR: A novel bispecific chimeric antigen receptor for cancer immunotherapy. Mol Ther Nucleic Acids 2: e105.
32. Lanitis, E, Poussin, M, Klattenhoff, AW, Song, D, Sandaltzopoulos, R, June, CH et al. (2013). Chimeric antigen receptor T cells with dissociated signaling domains exhibit focused antitumor activity with reduced potential for toxicity in vivo. Cancer Immunol Res 1: 43-53.
33. Fedorov, VD, Themeli, M and Sadelain, M (2013). PD-1-and CTLA-4-based inhibitory chimeric antigen receptors (iCARs) divert off-target immunotherapy responses. Sci Transl Med 5: 215ra172.
34. Fedorov, VD, Sadelain, M and Kloss, CC (2014). Novel approaches to enhance the specificity and safety of engineered T cells. Cancer J 20: 160-165.
35. Brown, CE, Badie, B, Barish, ME, Weng, L, Ostberg, JR, Chang, WC et al. (2015). Bioactivity and safety of IL13R2-redirected chimeric antigen receptor CD8+ T cells in patients with recurrent glioblastoma. Clin Cancer Res 21: 4062-4072.
36. Urbanska, K, Lanitis, E, Poussin, M, Lynn, RC, Gavin, BP, Kelderman, S et al. (2012). A universal strategy for adoptive immunotherapy of cancer through use of a novel T-cell antigen receptor. Cancer Res 72: 1844-1852.
37. Tamada, K, Geng, D, Sakoda, Y, Bansal, N, Srivastava, R, Li, Z et al. (2012). Redirecting genemodified T cells toward various cancer types using tagged antibodies. Clin Cancer Res 18: 6436-6445.
38. James, SE, Greenberg, PD, Jensen, MC, Lin, Y, Wang, J, Till, BG et al. (2008). Antigen sensitivity of CD22-specific chimeric TCR is modulated by target epitope distance from the cell membrane. J Immunol 180: 7028-7038.
39. Haso, W, Lee, DW, Shah, NN, Stetler-Stevenson, M, Yuan, CM, Pastan, IH et al. (2013). Anti-CD22-chimeric antigen receptors targeting B-cell precursor acute lymphoblastic leukemia. Blood 121: 1165-1174.
40. Guest, RD, Hawkins, RE, Kirillova, N, Cheadle, EJ, Arnold, J, O'Neill, A et al. (2005). The role of extracellular spacer regions in the optimal design of chimeric immune receptors: evaluation of four different scFvs and antigens. J Immunother 28: 203-211.
41. Hudecek, M, Sommermeyer, D, Kosasih, PL, Silva-Benedict, A, Liu, L, Rader, C et al. (2015). The nonsignaling extracellular spacer domain of chimeric antigen receptors is decisive for in vivo antitumor activity. Cancer Immunol Res 3: 125-135.
42. Hombach, A, Hombach, AA and Abken, H (2010). Adoptive immunotherapy with genetically engineered T cells: modification of the IgG1 Fc 'spacer' domain in the extracellular moiety of chimeric antigen receptors avoids 'off-target' activation and unintended initiation of an innate immune response. Gene Ther 17: 1206-1213.
43. Jonnalagadda, M, Mardiros, A, Urak, R, Wang, X, Hoffman, LJ, Bernanke, A et al. (2015). Chimeric antigen receptors with mutated IgG4 Fc spacer avoid fc receptor binding and improve T cell persistence and antitumor efficacy. Mol Ther 23: 757-768.
44. Almasbak, H, Walseng, E, Kristian, A, Myhre, MR, Suso, EM, Munthe, LA et al. (2015). Inclusion of an IgG1-Fc spacer abrogates efficacy of CD19 CAR T cells in a xenograft mouse model. Gene Ther 22: 391-403.
45. Savoldo, B, Ramos, CA, Liu, E, Mims, MP, Keating, MJ, Carrum, G et al. (2011). CD28 costimulation improves expansion and persistence of chimeric antigen receptormodified T cells in lymphoma patients. J Clin Invest 121: 1822-1826.
46. Porter, DL, Hwang, WT, Frey, NV, Lacey, SF, Shaw, PA, Loren, AW et al. (2015). Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med 7: 303ra139.
47. Tammana, S, Huang, X, Wong, M, Milone, MC, Ma, L, Levine, BL et al. (2010). 4-1BB and CD28 signaling plays a synergistic role in redirecting umbilical cord blood T cells against B-cell malignancies. Hum Gene Ther 21: 75-86.
48. Long, AH, Haso, WM, Shern, JF, Wanhainen, KM, Murgai, M, Ingaramo, M et al. (2015). 4-1BB costimulation ameliorates T cell exhaustion induced by tonic signaling of chimeric antigen receptors. Nat Med 21: 581-590.
49. Hombach, AA, Chmielewski, M, Rappl, G and Abken, H (2013). Adoptive immunotherapy with redirected T cells produces CCR7-cells that are trapped in the periphery and benefit from combined CD28-OX40 costimulation. Hum Gene Ther 24: 259-269.
50. Hombach, AA, Heiders, J, Foppe, M, Chmielewski, M and Abken, H (2012). OX40 costimulation by a chimeric antigen receptor abrogates CD28 and IL-2 induced IL-10 secretion by redirected CD4(+) T cells. Oncoimmunology 1: 458-466.
51. Guedan, S, Chen, X, Madar, A, Carpenito, C, McGettigan, SE, Frigault, MJ et al. (2014). ICOS-based chimeric antigen receptors program bipolar TH17/TH1 cells. Blood 124: 1070-1080.
52. Duong, CP, Westwood, JA, Yong, CS, Murphy, A, Devaud, C, John, LB et al. (2013). Engineering T cell function using chimeric antigen receptors identified using a DNA library approach. PLoS One 8: e63037.
53. Töpfer, K, Cartellieri, M, Michen, S, Wiedemuth, R, Müller, N, Lindemann, D et al. (2015). DAP12-based activating chimeric antigen receptor for NK cell tumor immunotherapy. J Immunol 194: 3201-3212.
54. Wang, E, Wang, LC, Tsai, CY, Bhoj, V, Gershenson, Z, Moon, E et al. (2015). Generation of potent T-cell immunotherapy for cancer using DAP12-based, multichain, chimeric immunoreceptors. Cancer Immunol Res 3: 815-826.
55. Abate-Daga, D, Hanada, K, Davis, JL, Yang, JC, Rosenberg, SA and Morgan, RA (2013). Expression profiling of TCR-engineered T cells demonstrates overexpression of multiple inhibitory receptors in persisting lymphocytes. Blood 122: 1399-1410.
56. Di Stasi, A, De Angelis, B, Rooney, CM, Zhang, L, Mahendravada, A, Foster, AE et al. (2009). T lymphocytes coexpressing CCR4 and a chimeric antigen receptor targeting CD30 have improved homing and antitumor activity in a Hodgkin tumor model. Blood 113: 6392-6402.
57. Zhao, Z, Condomines, M, van der Stegen, SJ, Perna, F, Kloss, CC, Gunset, G et al. (2015). Structural design of engineered costimulation determines tumor rejection kinetics and persistence of CAR T cells. Cancer Cell 28: 415-428.
58. Condomines, M, Arnason, J, Benjamin, R, Gunset, G, Plotkin, J and Sadelain, M (2015). Tumor-targeted human T cells expressing CD28-based chimeric antigen receptors circumvent CTLA-4 inhibition. PLoS One 10: e0130518.
59. Curran, KJ, Seinstra, BA, Nikhamin, Y, Yeh, R, Usachenko, Y, van Leeuwen, DG et al. (2015). Enhancing antitumor efficacy of chimeric antigen receptor T cells through constitutive CD40L expression. Mol Ther 23: 769-778.
60. Hoyos, V, Savoldo, B, Quintarelli, C, Mahendravada, A, Zhang, M, Vera, J et al. (2010). Engineering CD19-specific T lymphocytes with interleukin-15 and a suicide gene to enhance their anti-lymphoma/leukemia effects and safety. Leukemia 24: 1160-1170.
61. Markley, JC and Sadelain, M (2010). IL-7 and IL-21 are superior to IL-2 and IL-15 in promoting human T cell-mediated rejection of systemic lymphoma in immunodeficient mice. Blood 115: 3508-3519.
62. Car, BD, Eng, VM, Lipman, JM and Anderson, TD (1999). The toxicology of interleukin-12: A review. Toxicol Pathol 27: 58-63.
63. Pegram, HJ, Lee, JC, Hayman, EG, Imperato, GH, Tedder, TF, Sadelain, M et al. (2012). Tumor-targeted T cells modified to secrete IL-12 eradicate systemic tumors without need for prior conditioning. Blood 119: 4133-4141.
64. Zhang, L, Feldman, SA, Zheng, Z, Chinnasamy, N, Xu, H, Nahvi, AV et al. (2012). Evaluation of retroviral vectors that mediate the inducible expression of IL-12 for clinical application. J Immunother 35: 430-439.
65. Chmielewski, M, Kopecky, C, Hombach, AA and Abken, H (2011). IL-12 release by engineered T cells expressing chimeric antigen receptors can effectively Muster an antigen-independent macrophage response on tumor cells that have shut down tumor antigen expression. Cancer Res 71: 5697-5706.
66. Chinnasamy, D, Yu, Z, Kerkar, SP, Zhang, L, Morgan, RA, Restifo, NP et al. (2012). Local delivery of interleukin-12 using T cells targeting VEGF receptor-2 eradicates multiple vascularized tumors in mice. Clin Cancer Res 18: 1672-1683.
67. Zhang, L, Morgan, RA, Beane, JD, Zheng, Z, Dudley, ME, Kassim, SH et al. (2015). Tumorinfiltrating lymphocytes genetically engineered with an inducible gene encoding interleukin-12 for the immunotherapy of metastatic melanoma. Clin Cancer Res 21: 2278-2288.
68. Wang, X, Chang, WC, Wong, CW, Colcher, D, Sherman, M, Ostberg, JR et al. (2011). A transgene-encoded cell surface polypeptide for selection, in vivo tracking, and ablation of engineered cells. Blood 118: 1255-1263.
69. Jones, BS, Lamb, LS, Goldman, F and Di Stasi, A (2014). Improving the safety of cell therapy products by suicide gene transfer. Front Pharmacol 5: 254.
70. Fan, L, Freeman, KW, Khan, T, Pham, E and Spencer, DM (1999). Improved artificial death switches based on caspases and FADD. Hum Gene Ther 10: 2273-2285.
71. Di Stasi, A, Tey, SK, Dotti, G, Fujita, Y, Kennedy-Nasser, A, Martinez, C et al. (2011). Inducible apoptosis as a safety switch for adoptive cell therapy. N Engl J Med 365: 1673-1683.
72. Wu, CY, Roybal, KT, Puchner, EM, Onuffer, J and Lim, WA (2015). Remote control of therapeutic T cells through a small molecule-gated chimeric receptor. Science 350: Aab4077.