Function of Novel Anti-CD19 Chimeric Antigen Receptors with Human Variable Regions Is Affected by Hinge and Transmembrane Domains

Molecular Therapy

Volumn 25, Issue 11, 2017, Pages 2452-2465

  Alabanza, Leah ^a   Pegues, Melissa ^a   Geldres, Claudia ^a   Shi, Victoria ^a   Wiltzius, Jed J W ^b   Sievers, Stuart A ^b   Yang, Shicheng ^a   Kochenderfer, James N ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

^b Kite Pharma Inc   (United States)

Author keywords

chimeric antigen receptor; immunotherapy; T cell

Indexed keywords

CD19 ANTIBODY; CD19 ANTIGEN; CD28 ANTIGEN; CD8ALPHA ANTIGEN; CHIMERIC ANTIGEN RECEPTOR; CYTOKINE; MEMBRANE PROTEIN; SINGLE CHAIN FRAGMENT VARIABLE ANTIBODY; CD19 MOLECULE, HUMAN; CD8 ANTIGEN; CD8 ANTIGEN, ALPHA CHAIN; FUSION PROTEIN; LYMPHOCYTE ANTIGEN RECEPTOR;

ACTIVATION INDUCED CELL DEATH; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELL DEATH; CONTROLLED STUDY; CYTOKINE RELEASE; HINGE REGION; HUMAN; HUMAN CELL; LYMPHOCYTE PROLIFERATION; MOUSE; NONHUMAN; PROTEIN DOMAIN; PROTEIN EXPRESSION; T LYMPHOCYTE; TARGET CELL; ADOPTIVE IMMUNOTHERAPY; AMINO ACID SEQUENCE; ANIMAL; CHEMISTRY; CHRONIC LYMPHATIC LEUKEMIA; CYTOLOGY; DRUG SCREENING; GENE EXPRESSION; GENETIC TRANSDUCTION; GENETICS; IMMUNOLOGY; LYMPHOCYTE TRANSFUSION; METABOLISM; PATHOLOGY; PLASMID; PROCEDURES; SURVIVAL ANALYSIS; TRANSPLANTATION; TUMOR CELL LINE; TUMOR VOLUME;

AMINO ACID SEQUENCE; ANIMALS; ANTIGENS, CD19; CD28 ANTIGENS; CD8 ANTIGENS; CELL LINE, TUMOR; GENE EXPRESSION; HUMANS; IMMUNOTHERAPY, ADOPTIVE; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; LYMPHOCYTE TRANSFUSION; MICE; PLASMIDS; PROTEIN DOMAINS; RECEPTORS, ANTIGEN, T-CELL; RECOMBINANT FUSION PROTEINS; SINGLE-CHAIN ANTIBODIES; SURVIVAL ANALYSIS; T-LYMPHOCYTES; TRANSDUCTION, GENETIC; TUMOR BURDEN; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 85028356935     PISSN: 15250016     EISSN: 15250024     Source Type: Journal    
DOI: 10.1016/j.ymthe.2017.07.013     Document Type: Article

References (56)

1. Dotti, G., Gottschalk, S., Savoldo, B., Brenner, M.K., Design and development of therapies using chimeric antigen receptor-expressing T cells. Immunol. Rev. 257 (2014), 107–126.
2. Jensen, M.C., Riddell, S.R., Designing chimeric antigen receptors to effectively and safely target tumors. Curr. Opin. Immunol. 33 (2015), 9–15.
3. Kochenderfer, J.N., Rosenberg, S.A., Treating B-cell cancer with T cells expressing anti-CD19 chimeric antigen receptors. Nat. Rev. Clin. Oncol. 10 (2013), 267–276.
4. Sadelain, M., CAR therapy: the CD19 paradigm. J. Clin. Invest. 125 (2015), 3392–3400.
5. Eshhar, Z., Waks, T., Gross, G., Schindler, D.G., 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 90 (1993), 720–724.
6. Geldres, C., Savoldo, B., Dotti, G., Chimeric antigen receptor-redirected T cells return to the bench. Semin. Immunol. 28 (2016), 3–9.
7. Porter, D.L., Levine, B.L., Kalos, M., Bagg, A., June, C.H., Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N. Engl. J. Med. 365 (2011), 725–733.
8. Kochenderfer, J.N., Wilson, W.H., Janik, J.E., Dudley, M.E., Stetler-Stevenson, M., Feldman, S.A., Maric, I., Raffeld, M., Nathan, D.A., Lanier, B.J., et al. Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. Blood 116 (2010), 4099–4102.
9. Kochenderfer, J.N., Dudley, M.E., Feldman, S.A., Wilson, W.H., Spaner, D.E., Maric, I., Stetler-Stevenson, M., Phan, G.Q., Hughes, M.S., Sherry, R.M., et al. 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 (2012), 2709–2720.
10. Kochenderfer, J.N., Dudley, M.E., Kassim, S.H., Somerville, R.P.T., Carpenter, R.O., Stetler-Stevenson, M., Yang, J.C., Phan, G.Q., Hughes, M.S., Sherry, R.M., 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. 33 (2015), 540–549.
11. Turtle, C.J., Hanafi, L.A., Berger, C., Gooley, T.A., Cherian, S., Hudecek, M., Sommermeyer, D., Melville, K., Pender, B., Budiarto, T.M., et al. CD19 CAR-T cells of defined CD4+:CD8+ composition in adult B cell ALL patients. J. Clin. Invest. 126 (2016), 2123–2138.
12. Brentjens, R.J., Davila, M.L., Riviere, I., Park, J., Wang, X., Cowell, L.G., 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., 5, 2013, 177ra38.
13. Savoldo, B., Ramos, C.A., Liu, E., Mims, M.P., Keating, M.J., Carrum, G., Kamble, R.T., Bollard, C.M., Gee, A.P., Mei, Z., et al. CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients. J. Clin. Invest. 121 (2011), 1822–1826.
14. Lee, D.W., Kochenderfer, J.N., Stetler-Stevenson, M., Cui, Y.K., Delbrook, C., Feldman, S.A., Fry, T.J., Orentas, R., Sabatino, M., Shah, N.N., 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 385 (2015), 517–528.
15. Maude, S.L., Frey, N., Shaw, P.A., Aplenc, R., Barrett, D.M., Bunin, N.J., Chew, A., Gonzalez, V.E., Zheng, Z., Lacey, S.F., et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N. Engl. J. Med. 371 (2014), 1507–1517.
16. Davila, M.L., Riviere, I., Wang, X., Bartido, S., Park, J., Curran, K., Chung, S.S., 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., 6, 2014, 224ra25.
17. Turtle, C.J., Hanafi, L.A., 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., 8, 2016, 355ra116.
18. Kebriaei, P., Singh, H., Huls, M.H., Figliola, M.J., Bassett, R., Olivares, S., Jena, B., Dawson, M.J., Kumaresan, P.R., Su, S., et al. Phase I trials using Sleeping Beauty to generate CD19-specific CAR T cells. J. Clin. Invest. 126 (2016), 3363–3376.
19. Brudno, J.N., Somerville, R.P.T., Shi, V., Rose, J.J., Halverson, D.C., Fowler, D.H., Gea-Banacloche, J.C., Pavletic, S.Z., Hickstein, D.D., Lu, T.L., et al. Allogeneic T cells that express an anti-CD19 chimeric antigen receptor induce remissions of B-cell malignancies that progress after allogeneic hematopoietic stem-cell transplantation without causing graft-versus-host disease. J. Clin. Oncol. 34 (2016), 1112–1121.
20. Ali, S.A., Shi, V., Maric, I., Wang, M., Stroncek, D.F., Rose, J.J., Brudno, J.N., Stetler-Stevenson, M., Feldman, S.A., Hansen, B.G., et al. T cells expressing an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of multiple myeloma. Blood 128 (2016), 1688–1700.
21. Cruz, C.R.Y., Micklethwaite, K.P., Savoldo, B., Ramos, C.A., Lam, S., Ku, S., Diouf, O., Liu, E., Barrett, A.J., Ito, S., et al. Infusion of donor-derived CD19-redirected virus-specific T cells for B-cell malignancies relapsed after allogeneic stem cell transplant: a phase 1 study. Blood 122 (2013), 2965–2973.
22. Jensen, M.C., Popplewell, L., Cooper, L.J., DiGiusto, D., Kalos, M., Ostberg, J.R., Forman, S.J., 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 (2010), 1245–1256.
23. Lamers, C.H.J., Willemsen, R., van Elzakker, P., van Steenbergen-Langeveld, S., Broertjes, M., Oosterwijk-Wakka, J., Oosterwijk, E., Sleijfer, S., Debets, R., Gratama, J.W., Immune responses to transgene and retroviral vector in patients treated with ex vivo-engineered T cells. Blood 117 (2011), 72–82.
24. Sommermeyer, D., Hill, T., Shamah, S.M., Salter, A.I., Chen, Y., Mohler, K.M., Riddell, S.R., Fully human CD19-specific chimeric antigen receptors for T-cell therapy. Leukemia, 2017, 10.1038/leu.2017.57 Published online March 21, 2017.
25. Maher, J., Brentjens, R.J., Gunset, G., Rivière, I., Sadelain, M., Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCRzeta /CD28 receptor. Nat. Biotechnol. 20 (2002), 70–75.
26. Sadelain, M., Brentjens, R., Rivière, I., The basic principles of chimeric antigen receptor design. Cancer Discov. 3 (2013), 388–398.
27. Guest, R.D., Hawkins, R.E., Kirillova, N., Cheadle, E.J., Arnold, J., O'Neill, A., Irlam, J., Chester, K.A., Kemshead, J.T., Shaw, D.M., et al. The role of extracellular spacer regions in the optimal design of chimeric immune receptors: evaluation of four different scFvs and antigens. J. Immunother. 28 (2005), 203–211.
28. Gargett, T., Yu, W., Dotti, G., Yvon, E.S., Christo, S.N., Hayball, J.D., Lewis, I.D., Brenner, M.K., Brown, M.P., GD2-specific CAR T cells undergo potent activation and deletion following antigen encounter but can be protected from activation-induced cell death by PD-1 blockade. Mol. Ther. 24 (2016), 1135–1149.
29. Hudecek, M., Sommermeyer, D., Kosasih, P.L., Silva-Benedict, A., Liu, L., Rader, C., Jensen, M.C., Riddell, S.R., The nonsignaling extracellular spacer domain of chimeric antigen receptors is decisive for in vivo antitumor activity. Cancer Immunol. Res. 3 (2015), 125–135.
30. Künkele, A., Johnson, A.J., Rolczynski, L.S., Chang, C.A., Hoglund, V., Kelly-Spratt, K.S., Jensen, M.C., Functional tuning of CARs reveals signaling threshold above which CD8+ CTL antitumor potency is attenuated due to cell Fas-FasL-dependent AICD. Cancer Immunol. Res. 3 (2015), 368–379.
31. Brenner, D., Krammer, P.H., Arnold, R., Concepts of activated T cell death. Crit. Rev. Oncol. Hematol. 66 (2008), 52–64.
32. Green, D.R., Droin, N., Pinkoski, M., Activation-induced cell death in T cells. Immunol. Rev. 193 (2003), 70–81.
33. Brudno, J.N., Kochenderfer, J.N., Toxicities of chimeric antigen receptor T cells: recognition and management. Blood 127 (2016), 3321–3330.
34. Long, A.H., Haso, W.M., Shern, J.F., Wanhainen, K.M., Murgai, M., Ingaramo, M., Smith, J.P., Walker, A.J., Kohler, M.E., Venkateshwara, V.R., et al. 4-1BB costimulation ameliorates T cell exhaustion induced by tonic signaling of chimeric antigen receptors. Nat. Med. 21 (2015), 581–590.
35. Sallusto, F., Lenig, D., Förster, R., Lipp, M., Lanzavecchia, A., Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature 401 (1999), 708–712.
36. Wherry, E.J., Kurachi, M., Molecular and cellular insights into T cell exhaustion. Nat. Rev. Immunol. 15 (2015), 486–499.
37. Combadière, B., Freedman, M., Chen, L., Shores, E.W., Love, P., Lenardo, M.J., Qualitative and quantitative contributions of the T cell receptor zeta chain to mature T cell apoptosis. J. Exp. Med. 183 (1996), 2109–2117.
38. Kochenderfer, J.N., Yu, Z., Frasheri, D., Restifo, N.P., Rosenberg, S.A., Adoptive transfer of syngeneic T cells transduced with a chimeric antigen receptor that recognizes murine CD19 can eradicate lymphoma and normal B cells. Blood 116 (2010), 3875–3886.
39. Zhao, Y., Wang, Q.J., Yang, S., Kochenderfer, J.N., Zheng, Z., Zhong, X., Sadelain, M., Eshhar, Z., Rosenberg, S.A., Morgan, R.A., A herceptin-based chimeric antigen receptor with modified signaling domains leads to enhanced survival of transduced T lymphocytes and antitumor activity. J. Immunol. 183 (2009), 5563–5574.
40. Evans, E.J., Esnouf, R.M., Manso-Sancho, R., Gilbert, R.J.C., James, J.R., Yu, C., Fennelly, J.A., Vowles, C., Hanke, T., Walse, B., et al. Crystal structure of a soluble CD28-Fab complex. Nat. Immunol. 6 (2005), 271–279.
41. Leahy, D.J., Axel, R., Hendrickson, W.A., Crystal structure of a soluble form of the human T cell coreceptor CD8 at 2.6 A resolution. Cell 68 (1992), 1145–1162.
42. Pageon, S.V., Tabarin, T., Yamamoto, Y., Ma, Y., Bridgeman, J.S., Cohnen, A., Benzing, C., Gao, Y., Crowther, M.D., Tungatt, K., et al. Functional role of T-cell receptor nanoclusters in signal initiation and antigen discrimination. Proc. Natl. Acad. Sci. U S A 113 (2016), E5454–E5463.
43. van der Merwe, P.A., Dushek, O., Mechanisms for T cell receptor triggering. Nat. Rev. Immunol. 11 (2011), 47–55.
44. Whitlow, M., Bell, B.A., Feng, S.L., Filpula, D., Hardman, K.D., Hubert, S.L., Rollence, M.L., Wood, J.F., Schott, M.E., Milenic, D.E., et al. An improved linker for single-chain Fv with reduced aggregation and enhanced proteolytic stability. Protein Eng. 6 (1993), 989–995.
45. Kochenderfer, J.N., Dudley, M.E., Carpenter, R.O., Kassim, S.H., Rose, J.J., Telford, W.G., Hakim, F.T., Halverson, D.C., Fowler, D.H., Hardy, N.M., et al. Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation. Blood 122 (2013), 4129–4139.
46. Wherry, E.J., T cell exhaustion. Nat. Immunol. 12 (2011), 492–499.
47. Klebanoff, C.A., Gattinoni, L., Palmer, D.C., Muranski, P., Ji, Y., Hinrichs, C.S., Borman, Z.A., Kerkar, S.P., Scott, C.D., Finkelstein, S.E., et al. Determinants of successful CD8+ T-cell adoptive immunotherapy for large established tumors in mice. Clin. Cancer Res. 17 (2011), 5343–5352.
48. Chinnasamy, D., Yu, Z., Theoret, M.R., Zhao, Y., Shrimali, R.K., Morgan, R.A., Feldman, S.A., Restifo, N.P., Rosenberg, S.A., Gene therapy using genetically modified lymphocytes targeting VEGFR-2 inhibits the growth of vascularized syngenic tumors in mice. J. Clin. Invest. 120 (2010), 3953–3968.
49. Kochendefer, J.N., Somerville, R., Lu, T., Shi, V., Bot, A., Rossi, J., Xue, A., Goff, S.L., Yang, J.C., Sherry, R.M., et al. Lymphoma remissions caused by anti-CD19 chimeric antigen receptor t cells are associated with high serum inerleukin-15 levels. J. Clin. Oncol. 35 (2017), 1803–1813.
50. Eisenman, J., Ahdieh, M., Beers, C., Brasel, K., Kennedy, M.K., Le, T., Bonnert, T.P., Paxton, R.J., Park, L.S., Interleukin-15 interactions with interleukin-15 receptor complexes: characterization and species specificity. Cytokine 20 (2002), 121–129.
51. Carpenter, R.O., Evbuomwan, M.O., Pittaluga, S., Rose, J.J., Raffeld, M., Yang, S., Gress, R.E., Hakim, F.T., Kochenderfer, J.N., B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma. Clin. Cancer Res. 19 (2013), 2048–2060.
52. King, D.J., Rao-Naik, C., Pan, C., Cardarelli, J., and Blanset, D. April 2010. Human antibodies that bind CD19 and uses thereof. U.S. patent US2010/0104509 A1.
53. Yang, S., Dudley, M.E., Rosenberg, S.A., Morgan, R.A., A simplified method for the clinical-scale generation of central memory-like CD8+ T cells after transduction with lentiviral vectors encoding antitumor antigen T-cell receptors. J. Immunother. 33 (2010), 648–658.
54. Kochenderfer, J.N., Feldman, S.A., Zhao, Y., Xu, H., Black, M.A., Morgan, R.A., Wilson, W.H., Rosenberg, S.A., Construction and preclinical evaluation of an anti-CD19 chimeric antigen receptor. J. Immunother. 32 (2009), 689–702.
55. Hermans, I.F., Silk, J.D., Yang, J., Palmowski, M.J., Gileadi, U., McCarthy, C., Salio, M., Ronchese, F., Cerundolo, V., The VITAL assay: a versatile fluorometric technique for assessing CTL- and NKT-mediated cytotoxicity against multiple targets in vitro and in vivo. J. Immunol. Methods 285 (2004), 25–40.
56. Berman, H.M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T.N., Weissig, H., Shindyalov, I.N., Bourne, P.E., The Protein Data Bank. Nucleic Acids Res. 28 (2000), 235–242.