16,937
Views
8
CrossRef citations to date
0
Altmetric
Review

Axicabtagene ciloleucel, a first-in-class CAR T cell therapy for aggressive NHL

, , , &
Pages 1785-1796 | Received 02 Jun 2017, Accepted 26 Sep 2017, Published online: 23 Oct 2017

References

  • Yang Y. Cancer immunotherapy: harnessing the immune system to battle cancer. J Clin Invest. 2015;125:3335–3337.
  • Khalil DN, Smith EL, Brentjens RJ, et al. The future of cancer treatment: immunomodulation, CARs and combination immunotherapy. Nat Rev Clin Oncol. 2016;13:273–290.
  • Jackson HJ, Rafiq S, Brentjens RJ. Driving CAR T-cells forward. Nat Rev Clin Oncol. 2016;13:370–383.
  • Jensen MC, Riddell SR. Designing chimeric antigen receptors to effectively and safely target tumors. Curr Opin Immunol. 2015;33:9–15.
  • Priceman SJ, Forman SJ, Brown CE. Smart CARs engineered for cancer immunotherapy. Curr Opin Oncol. 2015;27:466–474.
  • Brentjens RJ, Curran KJ. Novel cellular therapies for leukemia: CAR-modified T cells targeted to the CD19 antigen. Hematol Am Soc Hematol Educ Program. 2012;2012:143–151.
  • Brentjens RJ, Riviere I, Park JH, et al. Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias. Blood. 2011;118:4817–4828.
  • Muranski P, Boni A, Wrzesinski C, et al. Increased intensity lymphodepletion and adoptive immunotherapy–how far can we go?. Nat Clin Pract Oncol. 2006;3:668–681.
  • Kochenderfer JN, Feldman SA, Zhao Y, et al. Construction and preclinical evaluation of an anti-CD19 chimeric antigen receptor. J Immunother. 2009;32:689–702.
  • Kochenderfer JN, Yu Z, Frasheri D, et al. Adoptive transfer of syngeneic T cells transduced with a chimeric antigen receptor that recognizes murine CD19 can eradicate lymphoma and normal B cells. Blood. 2010;116:3875–3886.
  • Kochenderfer JN, Wilson WH, Janik JE, 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. 2010;116:4099–4102.
  • Howlader NNA, Krapcho M, Miller D, et al., editors. SEER cancer statistics review, 1975–2013. Bethesda (MD): National Cancer Institute; 2017.
  • Chaganti S, Illidge T, Barrington S, et al. Guidelines for the management of diffuse large B-cell lymphoma. Br J Haematol. 2016;174:43–56.
  • Lossos IS, Gascoyne RD. Transformation of follicular lymphoma. Best Pract Res Clin Haematol. 2011;24:147–163.
  • Petkovic I. Current trends in the treatment of primary mediastinal large B-cell lymphoma – an overview. Contemp Oncol (Pozn). 2015;19:428–435.
  • Kridel R, Mottok A, Farinha P, et al. Cell of origin of transformed follicular lymphoma. Blood. 2015;126:2118–2127.
  • Tan D, Horning SJ, Hoppe RT, et al. Improvements in observed and relative survival in follicular grade 1–2 lymphoma during 4 decades: the Stanford University experience. Blood. 2013;122:981–987.
  • Provencio M, Sabin P, Gomez-Codina J, et al. Impact of treatment in long-term survival patients with follicular lymphoma: a Spanish Lymphoma Oncology Group registry. PLoS One. 2017;12:e0177204.
  • Dunleavy K, Wilson WH. Primary mediastinal B-cell lymphoma and mediastinal gray zone lymphoma: do they require a unique therapeutic approach? Blood. 2015;125:33–39.
  • Wagner-Johnston ND, Link BK, Byrtek M, et al. Outcomes of transformed follicular lymphoma in the modern era: a report from the National LymphoCare Study (NLCS). Blood. 2015;126:851–857.
  • Crump M, Neelapu SS, Farooq U, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017. [in press]. doi: 10.1182/blood-2017-03-769620
  • Gisselbrecht C, Glass B, Mounier N, et al. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. JCO. 2010;28:4184–4190.
  • Friedberg JW. Relapsed/refractory diffuse large B-cell lymphoma. Hematol Am Soc Hematol Educ Program. 2011;2011:498–505.
  • Jin Z, Maiti S, Huls H, et al. The hyperactive Sleeping Beauty transposase SB100X improves the genetic modification of T cells to express a chimeric antigen receptor. Gene Ther. 2011;18:849–856.
  • Till BG, Jensen MC, Wang J, et al. Adoptive immunotherapy for indolent non-Hodgkin lymphoma and mantle cell lymphoma using genetically modified autologous CD20-specific T cells. Blood. 2008;112:2261–2271.
  • Wang X, Riviere I. Clinical manufacturing of CAR T cells: foundation of a promising therapy. Mol Ther Oncolytics. 2016;3:16015.
  • Gattinoni L, Klebanoff CA, Restifo NP. Paths to stemness: building the ultimate antitumour T cell. Nat Rev Cancer. 2012;12:671–684.
  • Chodon T, Comin-Anduix B, Chmielowski B, et al. Adoptive transfer of MART-1 T-cell receptor transgenic lymphocytes and dendritic cell vaccination in patients with metastatic melanoma. Clin Cancer Res. 2014;20:2457–2465.
  • Better M, Chiruvolu V, Oliver J, et al. Manufacturing and characterization of KTE-C19 in a multicenter trial of subjects with refractory aggressive non-Hodgkin lymphoma (NHL) (ZUMA-1). Proceedings of the 105th Annual Meeting American Association Cancer Research; New Orleans (LA): AACR; 2015. p. 2308.
  • Better M, Chiruvolu V, Oliver J, et al. Production of KTE-C19 (anti-CD19 CAR T cells) for ZUMA-1: a phase 1/2 multi-center study evaluating safety and efficacy in subjects with refractory aggressive non-Hodgkin lymphoma (NHL). Mol Ther. 2016;24:287.
  • Klebanoff CA, Khong HT, Antony PA, et al. Sinks, suppressors and antigen presenters: how lymphodepletion enhances T cell-mediated tumor immunotherapy. Trends Immunol. 2005; 26:111–117.
  • Kochenderfer JN, Somerville RP, Lu T, et al. Lymphoma remissions caused by anti-CD19 chimeric antigen receptor T cells are associated with high serum Interleukin-15 levels. JCO. 2017;35:1803–1813.
  • Dudley ME, Yang JC, Sherry R, et al. Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens. JCO. 2008;26:5233–5239.
  • Dudley ME, Wunderlich JR, Robbins PF, et al. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science. 2002;298:850–854.
  • Kochenderfer JN, Dudley ME, Kassim SH, 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. JCO. 2015;33:540–549.
  • Turtle CJ, Hanafi LA, Berger C, 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;8:355ra116.
  • Siddiqi T, Neelapu S, Locke F, et al. Updated phase 1 results from ZUMA-1: a phase 1–2 multicenter study evaluating the safety and efficacy of KTE-C19 (anti-CD19 CAR T cells) in refractory aggressive B-cell non-Hodgkin lymphoma (NHL). Mol Ther. 2016;21:S791.
  • Kochenderfer JN, Dudley ME, Feldman SA, 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. 2012;119:2709–2720.
  • Kochenderfer JN, Somerville RPT, Lu T, et al. Long-duration complete remissions of diffuse large B cell lymphoma after anti-CD19 chimeric antigen receptor T cell therapy. Mol Ther. 2017;25:2245–2253.
  • Locke F, Neelapu S, Bartlett N, et al. Phase 1 results of ZUMA-1: a multicenter study of KTE-C19 anti-CD19 CAR T cell therapy in refractory aggressive lymphoma. Mol Ther. 2016;25:285–295.
  • Locke FL, Neelapu SS, Bartlett NL, et al. Primary results from ZUMA-1: a pivotal trial of axicabtagene ciloleucel (Axi-cel; KTE-C19) in patients with refractory aggressive non-Hodgkin lymphoma (NHL). Proceedings of the 107th Annual Meeting American Association Cancer Research; Washington (DC): AACR; 2017. p. CT019.
  • Wang M, Locke F, Siddiqi T, et al. ZUMA-2: a phase 2 multicenter study evaluating the efficacy of KTE-C19 (anti-CD19 CAR T cells) in patients with relapsed/refractory mantle cell lymphoma (R/R MCL). Ann Oncol. 2016;27:943TiP.
  • Wayne A, Sender L, Lee D, et al. ZUMA-4: a phase 1/2 multicenter study evaluating the safety and efficacy of KTE-C19 (anti-CD19 CAR T cells) in pediatric and adolescent subjects with relapsed/refractory B-precursor acute lymphoblastic leukemia (R/R ALL). J Clin Oncol. 2016;34:TPS7075.
  • Shah B, Castro J, Wierda W, et al. ZUMA-3: a phase 1/2 multicenter study evaluating the safety and efficacy of KTE-C19 (anti-CD19 CAR T cells) in adult patients with relapsed/refractory B precursor acute lymphoblastic leukemia (R/R ALL). Ann Oncol. 2016;27:415TiP.
  • Lee DW, Kochenderfer JN, Stetler-Stevenson M, 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. 2015;385:517–528.
  • Maude SL, Frey N, Shaw PA, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014;371:1507–1517.
  • Porter DL, Hwang WT, Frey NV, et al. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med. 2015;7:303ra139.
  • Bot A, Rossi J, Yizhou J, et al. Cyclophosphamide and fludarabine conditioning chemotherapy induces a key homeostatic cytokine profile in patients prior to CAR T cell therapy. ASH Ann Meeting Abstracts. 2015;126:4426.
  • Neelapu S, Locke F, Bartlett N, et al. Ongoing complete remissions (CR) in the phase 1 of ZUMA-1: a phase 1-2 multicenter study evaluating the safety and efficacy of KTE-C19 (anti-CD19 CAR T cells) in subjects with refractory aggressive B-cell non-Hodgkin lymphoma (NHL). Vol. 34. ASCO Annual Meeting; 2016; Chicago, IL.
  • Rossi J, Sherman M, Xue A, et al. Low dose conditioning chemotherapy and CD19-directed CAR T cells May elicit distinct immune programs associated with clinical responses. SITC Meeting Abstracts; 2016; Los Angeles, CA.
  • Bonifant C, Jackson H, Brentjens RJ, et al. Toxicity and management in CAR T-cell therapy. Mol Ther Oncolytics. 2016;3:16011.
  • Lee DW, Gardner R, Porter DL, et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014;124:188–195.
  • Benjamin JE, Stein AS. The role of blinatumomab in patients with relapsed/refractory acute lymphoblastic leukemia. Ther Adv Hematol. 2016;7:142–156.
  • Dai H, Wang Y, Lu X, et al. Chimeric antigen receptors modified T-cells for cancer therapy. J Natl Cancer Inst. 2016;108:pii:djv439.
  • Maude SL, Barrett D, Teachey DT, et al. Managing cytokine release syndrome associated with novel T cell-engaging therapies. Cancer J. 2014;20:119–122.
  • Maude SL, Teachey DT, Porter DL, et al. CD19-targeted chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia. Blood. 2015;125:4017–4023.
  • Gardner R, Leger K, Annesley C, et al. Decreased rates of severe CRS seen with early intervention strategies for CD19 CAR-T cell toxicity management. Blood. 2016:128:586.
  • Levine BL. Performance-enhancing drugs: design and production of redirected chimeric antigen receptor (CAR) T cells. Cancer Gene Ther. 2015;22:79–84.
  • Dunbar CE. Blood’s 70th anniversary: CARs on the blood highway. Blood. 2016;128:1–3.
  • Kalos M, Levine BL, Porter DL, et al. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med. 2011;3:95ra73.
  • Stancovski I, Schindler DG, Waks T, et al. Targeting of T lymphocytes to Neu/HER2-expressing cells using chimeric single chain Fv receptors. J Immunol. 1993;151:6577–6582.
  • Dotti G, Gottschalk S, Savoldo B, et al. Design and development of therapies using chimeric antigen receptor-expressing T cells. Immunol Rev. 2014;257:107–126.
  • Cao Y, Rodgers DT, Du J, et al. Design of switchable chimeric antigen receptor T cells targeting breast cancer. Angew Chem Int Ed. 2016;55:7520–7524.
  • Cartellieri M, Feldmann A, Koristka S, et al. Switching CAR T cells on and off: a novel modular platform for retargeting of T cells to AML blasts. Blood Cancer J. 2016;6:e458.
  • Rodgers DT, Mazagova M, Hampton EN, et al. Switch-mediated activation and retargeting of CAR-T cells for B-cell malignancies. Proc Natl Acad Sci USA. 2016;113:E459–E468.
  • Zah E, Lin MY, Silva-Benedict A, et al. ADDENDUM: T cells expressing CD19/CD20 bispecific chimeric antigen receptors prevent antigen escape by malignant B cells. Cancer Immunol Res. 2016;4:639–641.
  • Zah E, Lin MY, Silva-Benedict A, et al. T cells expressing CD19/CD20 bispecific chimeric antigen receptors prevent antigen escape by malignant B cells. Cancer Immunol Res. 2016;4:498–508.
  • Abate-Daga D, Hanada K, Davis JL, et al. Expression profiling of TCR-engineered T cells demonstrates overexpression of multiple inhibitory receptors in persisting lymphocytes. Blood. 2013;122:1399–1410.
  • Cherkassky L, Morello A, Villena-Vargas J, et al. Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition. J Clin Invest. 2016;126:3130–3144.
  • John LB, Kershaw MH, Darcy PK. Blockade of PD-1 immunosuppression boosts CAR T-cell therapy. Oncoimmunology. 2013;2:e26286.
  • Fraietta JA, Beckwith KA, Patel PR, et al. Ibrutinib enhances chimeric antigen receptor T-cell engraftment and efficacy in leukemia. Blood. 2016;127:1117–1127.