Third-generation CD28/4-1BB chimeric antigen receptor T cells for chemotherapy relapsed or refractory acute lymphoblastic leukaemia: A non-randomised, open-label phase i trial protocol

BMJ Open

Volumn 6, Issue 12, 2016, Pages

  Tang, Xiao Yi ^a   Sun, Yao ^a   Zhang, Ang ^a   Hu, Guo Liang ^a   Cao, Wei ^a   Wang, Dan Hong ^a   Zhang, Bin ^a   Chen, Hu ^a  

^a BEIJING INSTITUTE OF MICROBIOLOGY AND EPIDEMIOLOGY   (China)

Author keywords

acute lymphoblastic leukemia; chimeric antigen receptor; IMMUNOLOGY; Third generation

Indexed keywords

CD137 ANTIGEN; CD28 ANTIGEN; CHIMERIC ANTIGEN RECEPTOR; CYCLOPHOSPHAMIDE; DEXAMETHASONE; FLUDARABINE; GAMMA INTERFERON; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; INTERLEUKIN 2 RECEPTOR ALPHA; INTERLEUKIN 6; INTERLEUKIN 6 RECEPTOR; INTERLEUKIN 8; MACROPHAGE INFLAMMATORY PROTEIN 1ALPHA; MONOCYTE CHEMOTACTIC PROTEIN 1; LYMPHOCYTE ANTIGEN RECEPTOR; TNFRSF9 PROTEIN, HUMAN; TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY MEMBER 9;

ACUTE LYMPHOBLASTIC LEUKEMIA; ADULT; AGED; APLASIA; ARTICLE; B LYMPHOCYTE; CANCER CHEMOTHERAPY; CONTROLLED STUDY; CYTOKINE RELEASE SYNDROME; DISEASE SEVERITY; DRUG SAFETY; FEMALE; FLOW CYTOMETRY; HUMAN; HUMAN CELL; MALE; NEUROTOXICITY; OPEN STUDY; PERIPHERAL BLOOD MONONUCLEAR CELL; PHASE 1 CLINICAL TRIAL; PHENOTYPE; REAL TIME POLYMERASE CHAIN REACTION; T LYMPHOCYTE; TRANSGENE; ADOPTIVE IMMUNOTHERAPY; CLINICAL PROTOCOL; CLINICAL TRIAL; DRUG EFFECTS; IMMUNOLOGY; LYMPHOCYTE ACTIVATION; MIDDLE AGED; MONONUCLEAR CELL; PATHOPHYSIOLOGY; RECURRENT DISEASE; REMISSION; TUMOR CELL LINE;

ADULT; CD28 ANTIGENS; CELL LINE, TUMOR; CLINICAL PROTOCOLS; FEMALE; HUMANS; IMMUNOTHERAPY, ADOPTIVE; LEUKOCYTES, MONONUCLEAR; LYMPHOCYTE ACTIVATION; MALE; MIDDLE AGED; PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA; RECEPTORS, ANTIGEN, T-CELL; RECURRENCE; REMISSION INDUCTION; TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY, MEMBER 9;

EID: 85008485906     PISSN: None     EISSN: 20446055     Source Type: Journal    
DOI: 10.1136/bmjopen-2016-013904     Document Type: Article

References (43)

1. Pui CH, Robison LL, Look AT. Acute lymphoblastic leukaemia. Lancet 2008;371:1030-43.
2. Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 2010;363:411-22.
3. Palucka K, Banchereau J. Cancer immunotherapy via dendritic cells. Nat Rev Cancer 2012;12:265-77.
4. Hodi FS, O'Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010;363:711-23.
5. Robert C, Long GV, Brady B, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med 2015;372:320-30.
6. Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med 2015;372:2018-28.
7. Rosenberg JE, Hoffman-Censits J, Powles T, et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet 2016;387:1909-20.
8. June CH. Adoptive T cell therapy for cancer in the clinic. J Clin Invest 2007;117:1466-76.
9. Keppler SJ, Rosenits K, Koegl T, et al. Signal 3 cytokines as modulators of primary immune responses during infections: the interplay of type I IFN and IL-12 in CD8 T cell responses. PLoS ONE 2012;7:e40865.
10. Imai C, Mihara K, Andreansky M, et al. Chimeric receptors with 4-1BB signaling capacity provoke potent cytotoxicity against acute lymphoblastic leukemia. Leukemia 2004;18:676-84.
11. Kowolik CM, Topp MS, Gonzalez S, et al. CD28 costimulation provided through a CD19-specific chimeric antigen receptor enhances in vivo persistence and antitumor efficacy of adoptively transferred T cells. Cancer Res 2006;66:10995-1004.
12. Gross G, Waks T, Eshhar Z. Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity. Proc Natl Acad Sci USA 1989;86:10024-8.
13. Finney HM, Akbar AN, Lawson AD. Activation of resting human primary T cells with chimeric receptors: costimulation from CD28, inducible costimulator, CD134, and CD137 in series with signals from the TCR zeta chain. J Immunol 2004;172:104-13.
14. Milone MC, Fish JD, Carpenito C, et al. Chimeric receptors containing CD137 signal transduction domains mediate enhanced survival of T cells and increased antileukemic efficacy in vivo. Mol Ther 2009;17:1453-64.
15. Gardner RA, Finney O, Smithers H, et al. Prolonged functional persistence of CD19CAR t cell products of defined CD4:CD8 composition and transgene expression determines durability of MRD-negative ALL remission. J ClinOncol 2016;34(Suppl); abstr 3048.
16. 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;118:4817-28.
17. Brentjens RJ, Davila ML, Riviere I, et al. CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci Transl Med 2013;5:177ra38.
18. Davila ML, Riviere I, Wang X, et al. Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci Transl Med 2014;6:224ra25.
19. Park JH, Riviere I, Wang X, 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;126:682.
20. 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;385:517-28.
21. Lee DW, Stetler-Stevenson M, Yuan CM, 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;126:684.
22. Brudno JN, Somerville RP, Shi V, 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 2016;34:1112-21.
23. Brudno JN, Somerville R, Shi V, et al. Allogeneic T-cells expressing an anti-CD19 chimeric antigen receptor cause remissions of B-cell malignancies after allogeneic hematopoietic stem cell transplantation without causing graft-versus-host disease. Blood 2015;126:99.
24. Maude SL, Frey N, Shaw PA, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med 2014;371:1507-17.
25. Maude SL, Teachey DT, Rheingold SR, et al. Sustained remissions with CD19-specific chimeric antigen receptor (CAR)-modified T cells in children with relapsed/refractory ALL. J Clin Oncol 2016;34 (Suppl); abstr 3011.
26. Maude SL, Barrett DM, Rheingold SR, et al. Efficacy of humanized CD19-targeted chimeric antigen receptor (CAR)-modified T cells in children with relapsed ALL. J Clin Oncol 2016;34(Suppl); abstr 3007.
27. Cruz CR, Micklethwaite KP, Savoldo B, 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 2013;122:2965-73.
28. Dai H, Zhang W, Li X, et al. Tolerance and efficacy of autologous or donor-derived T cells expressing CD19 chimeric antigen receptors in adult B-ALL with extramedullary leukemia. Oncoimmunology 2015;4: e1027469.
29. Turtle CJ, Hanafi LA, Berger C, et al. CD19 CAR-T cells of defined CD4+:CD8+ composition in adult B cell ALL patients. J Clin Invest 2016;126:2123-38.
30. Turtle CJ, Hanafi LA, Berger C, et al. Rate of durable complete response in ALL, NHL, and CLL after immunotherapy with optimized lymphodepletion and defined composition CD19 CAR-T cells. J Clin Oncol 2016;34(Suppl); abstr 102.
31. Kebriaei P, Singh H, Huls MH, et al. Phase I trials using Sleeping Beauty to generate CD19-specific CAR T cells. J Clin Invest 2016;126:3363-76.
32. Hu Y, Sun J, Wu Z, et al. Predominant cerebral cytokine release syndrome in CD19-directed chimeric antigen receptor-modified T cell therapy. J Hematol Oncol 2016;9:70.
33. Dong L, Chang L, Gao Z, et al. Chimeric antigen receptor 4SCAR19-modified T cells in acute lymphoid leukemia: a phase II multi-center clinical trial in China. Blood 2015;126:3774.
34. van der Stegen SJ, Hamieh M, Sadelain M. The pharmacology of second-generation chimeric antigen receptors. Nat Rev Drug Discov 2015;14:499-509.
35. Karlsson H, Svensson E, Gigg C, et al. Evaluation of intracellular signaling downstream chimeric antigen receptors. PLoS ONE 2015;10:e0144787.
36. Lee DW, Gardner R, Porter DL, et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood 2014;124:188-95.
37. Brudno JN, Kochenderfer JN. Toxicities of chimeric antigen receptor T cells: recognition and management. Blood 2016;127:3321-30.
38. Frey NV, Luger SM. How I treat adults with relapsed or refractory Philadelphia chromosome-negative acute lymphoblastic leukemia. Blood 2015;126:589-96.
39. Haso W, Lee DW, Shah NN, et al. Anti-CD22-chimeric antigen receptors targeting B-cell precursor acute lymphoblastic leukemia. Blood 2013;121:1165-74.
40. Kochenderfer JN, Rosenberg SA. Treating B-cell cancer with T cells expressing anti-CD19 chimeric antigen receptors. Nat Rev Clin Oncol 2013;10:267-76.
41. Kalaitsidou M, Kueberuwa G, Schutt A, et al. CAR T-cell therapy: toxicity and the relevance of preclinical models. Immunotherapy 2015;7:487-97.
42. Teachey DT, Lacey SF, Shaw PA, et al. Identification of predictive biomarkers for cytokine release syndrome after chimeric antigen receptor t-cell therapy for acute lymphoblastic leukemia. Cancer Discov 2016;6:664-79.
43. Bai Y, Kan S, Zhou S, et al. Enhancement of the in vivo persistence and antitumor efficacy of CD19 chimeric antigen receptor T cells through the delivery of modified TERT mRNA. Cell Discov 2015;1:15040.