Recent advances in CAR T-cell toxicity: Mechanisms, manifestations and management

Blood Reviews - Tập 34 - Trang 45-55 - 2019
Jennifer N. Brudno1, James N. Kochenderfer1
1Experimental Transplantation and Immunology Branch, National Cancer Institute, Building 10, Suite 3-3330, Bethesda, MD 20892, United States

Tóm tắt

Từ khóa


Tài liệu tham khảo

Eshhar, 1993, 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, 720, 10.1073/pnas.90.2.720

Kochenderfer, 2013, Treating B-cell cancer with T cells expressing anti-CD19 chimeric antigen receptors, Nat Rev Clin Oncol, 10, 267, 10.1038/nrclinonc.2013.46

Sadelain, 2013, The basic principles of chimeric antigen receptor design, Cancer Discov, 3, 388, 10.1158/2159-8290.CD-12-0548

Johnson, 2017, Driving gene-engineered T cell immunotherapy of cancer, Cell Res, 27, 38, 10.1038/cr.2016.154

Rouce, 2017, Recent advances in T-cell immunotherapy for haematological malignancies, Br J Haematol, 176, 688, 10.1111/bjh.14470

June, 2018, Chimeric antigen receptor therapy, N Engl J Med, 379, 64, 10.1056/NEJMra1706169

Maude, 2014, Chimeric antigen receptor T cells for sustained remissions in leukemia, N Engl J Med, 371, 1507, 10.1056/NEJMoa1407222

Lee, 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, 10.1016/S0140-6736(14)61403-3

Turtle, 2016, CD19 CAR-T cells of defined CD4+:CD8+ composition in adult B cell ALL patients, J Clin Invest, 126, 2123, 10.1172/JCI85309

Brentjens, 2013, CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia, Sci Transl Med, 5, 177ra38, 10.1126/scitranslmed.3005930

Davila, 2014, Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia, Sci Transl Med, 6, 224ra25, 10.1126/scitranslmed.3008226

Maude, 2018, Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia, N Engl J Med, 378, 439, 10.1056/NEJMoa1709866

Park, 2018, Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia, N Engl J Med, 378, 449, 10.1056/NEJMoa1709919

Porter, 2015, Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia, Sci Transl Med, 7, 303ra139, 10.1126/scitranslmed.aac5415

Turtle, 2017, Durable molecular remissions in chronic lymphocytic leukemia treated with CD19-specific chimeric antigen receptor-modified T cells after failure of ibrutinib, J Clin Oncol, 35, 3010, 10.1200/JCO.2017.72.8519

Porter, 2011, Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia, N Engl J Med, 365, 725, 10.1056/NEJMoa1103849

Fraietta, 2018, Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia, Nat Med, 24, 563, 10.1038/s41591-018-0010-1

Kochenderfer, 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, 10.1182/blood-2011-10-384388

Kochenderfer, 2015, 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, 540, 10.1200/JCO.2014.56.2025

Turtle, 2016, 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, 355ra116, 10.1126/scitranslmed.aaf8621

Kochenderfer, 2017, Lymphoma remissions caused by anti-CD19 chimeric antigen receptor T cells are associated with high serum interleukin-15 levels, J Clin Oncol, 35, 1803, 10.1200/JCO.2016.71.3024

Locke, 2017, Phase 1 results of ZUMA-1: a multicenter study of KTE-C19 Anti-CD19 CAR T cell therapy in refractory aggressive lymphoma, Mol Ther, 25, 285, 10.1016/j.ymthe.2016.10.020

Kochenderfer, 2017, Long-duration complete remissions of diffuse large B cell lymphoma after anti-CD19 chimeric antigen receptor T cell therapy, Mol Ther, 25, 2245, 10.1016/j.ymthe.2017.07.004

Brudno, 2018, Chimeric antigen receptor T-cell therapies for lymphoma, Nat Rev Clin Oncol, 15, 31, 10.1038/nrclinonc.2017.128

Neelapu, 2017, Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma, N Engl J Med, 377, 2531, 10.1056/NEJMoa1707447

Schuster, 2017, Chimeric antigen receptor T cells in refractory B-cell lymphomas, N Engl J Med, 377, 2545, 10.1056/NEJMoa1708566

Abramson, 2018, Updated safety and long term clinical outcomes in TRANSCEND NhL 001, pivotal trial of lisocabtagene maraleucel (JCAR017) in R/R aggressive NHL

Schuster, 2017, Primary Analysis of JULIET, A Global, Pivotal, Phase 2 Trial of CTL019 in Adult Patients with Relapsed or Refractory Diffuse Large B-cell Lymphoma

Ali, 2016, T cells expressing an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of multiple myeloma, Blood, 128, 1688, 10.1182/blood-2016-04-711903

Brudno, 2018, T cells genetically modified to express an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of poor-prognosis relapsed multiple myeloma, J Clin Oncol, 36, 2267, 10.1200/JCO.2018.77.8084

Mikkilineni, 2017, Chimeric antigen receptor T-cell therapies for multiple myeloma, Blood, 130, 2594, 10.1182/blood-2017-06-793869

Wang, 2017, Autologous T cells expressing CD30 chimeric antigen receptors for relapsed or refractory hodgkin lymphoma: an open-Label phase I trial, Clin Cancer Res, 23, 1156, 10.1158/1078-0432.CCR-16-1365

Ramos, 2017, Clinical and immunological responses after CD30-specific chimeric antigen receptor-redirected lymphocytes, J Clin Invest, 127, 3462, 10.1172/JCI94306

Brown, 2016, Regression of glioblastoma after chimeric antigen receptor T-cell therapy, N Engl J Med, 375, 2561, 10.1056/NEJMoa1610497

Adusumilli, 2014, Regional delivery of mesothelin-targeted CAR T cell therapy generates potent and long-lasting CD4-dependent tumor immunity, Sci Transl Med, 6, 261ra151, 10.1126/scitranslmed.3010162

Louis, 2011, Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma, Blood, 118, 6050, 10.1182/blood-2011-05-354449

Ahmed, 2015, Human epidermal growth factor receptor 2 (HER2) -specific chimeric antigen receptor-modified T cells for the immunotherapy of HER2-positive sarcoma, J Clin Oncol, 33, 1688, 10.1200/JCO.2014.58.0225

FDA approval brings first gene therapy to the United States: CAR T-cell therapy approved to treat certain children and young adults with B-cell acute lymphoblastic leukemia. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm574058.htm. United States Food and Drug Administration Press ReleaseAugust 30, 2017.

FDA approves CAR-T cell therapy to treat adults with certain types of large B-cell lymphoma: Yescarta is the second gene therapy product approved in the U.S. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm581216.htm. United States Food and Drug Administration Press ReleaseOctober 18, 2017.

FDA approves tisagenlecleucel for adults with relapsed or refractory large B-cell lymphoma. https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm606540.htm. United States Food and Drug Administration Press ReleaseMay 1, 2018.

Brudno, 2016, Toxicities of chimeric antigen receptor T cells: recognition and management, Blood, 127, 3321, 10.1182/blood-2016-04-703751

Lee, 2014, Current concepts in the diagnosis and management of cytokine release syndrome, Blood, 124, 188, 10.1182/blood-2014-05-552729

Neelapu, 2018, Chimeric antigen receptor T-cell therapy - assessment and management of toxicities, Nat Rev Clin Oncol, 15, 47, 10.1038/nrclinonc.2017.148

Frey, 2017, Cytokine release syndrome: who is at risk and how to treat, Best Pract Res Clin Haematol, 30, 336, 10.1016/j.beha.2017.09.002

Brudno, 2016, 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, 1112, 10.1200/JCO.2015.64.5929

Teachey, 2016, Identification of predictive biomarkers for cytokine release syndrome after chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia, Cancer Discov, 6, 664, 10.1158/2159-8290.CD-16-0040

Fitzgerald, 2017, Cytokine release syndrome after chimeric antigen receptor T cell therapy for acute lymphoblastic leukemia, Crit Care Med, 45, e124, 10.1097/CCM.0000000000002053

Kochenderfer, 2013, Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation, Blood, 122, 4129, 10.1182/blood-2013-08-519413

Jensen, 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, 10.1016/j.bbmt.2010.03.014

Kochenderfer, 2010, Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19, Blood, 116, 4099, 10.1182/blood-2010-04-281931

Wang, 2014, Effective response and delayed toxicities of refractory advanced diffuse large B-cell lymphoma treated by CD20-directed chimeric antigen receptor-modified T cells, Clin Immunol, 155, 160, 10.1016/j.clim.2014.10.002

Santomasso, 2018, Clinical and biologic correlates of neurotoxicity associated with CAR T cell therapy in patients with B-cell acute lymphoblastic leukemia (B-ALL), Cancer Discov, 8, 958, 10.1158/2159-8290.CD-17-1319

Brooks, 2016, CAR T-Cell Leukemia Trial put on hold after two Deaths, Medscape Medical News

Hill, 2018, Infectious complications of CD19-targeted chimeric antigen receptor-modified T-cell immunotherapy, Blood, 131, 121, 10.1182/blood-2017-07-793760

Park, 2018, Cytokine release syndrome grade is a predictive marker for infections in relapsed or refractory B-cell all patients treated with CAR T cells, Clin Infect Dis, 67, 533, 10.1093/cid/ciy152

Gust, 2017, Endothelial activation and blood-brain barrier disruption in neurotoxicity after adoptive immunotherapy with CD19 CAR-T cells, Cancer Discov, 7, 1404, 10.1158/2159-8290.CD-17-0698

Gardner, 2017, Intent-to-treat leukemia remission by CD19 CAR T cells of defined formulation and dose in children and young adults, Blood, 129, 3322, 10.1182/blood-2017-02-769208

Hay, 2017, Kinetics and biomarkers of severe cytokine release syndrome after CD19 chimeric antigen receptor-modified T-cell therapy, Blood, 130, 2295, 10.1182/blood-2017-06-793141

Gattinoni, 2005, Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8+ T cells, J Exp Med, 202, 907, 10.1084/jem.20050732

Klebanoff, 2005, Sinks, suppressors and antigen presenters: how lymphodepletion enhances T cell-mediated tumor immunotherapy, Trends Immunol, 26, 111, 10.1016/j.it.2004.12.003

North, 1982, Cyclophosphamide-facilitated adoptive immunotherapy of an established tumor depends on elimination of tumor-induced suppressor T cells, J Exp Med, 155, 1063, 10.1084/jem.155.4.1063

Kochenderfer, 2010, 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, 3875, 10.1182/blood-2010-01-265041

Brentjens, 2011, Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias, Blood, 118, 4817, 10.1182/blood-2011-04-348540

Teachey, 2018, Toxicity management after chimeric antigen receptor T cell therapy: one size does not fit 'ALL', Nat Rev Clin Oncol, 15, 218, 10.1038/nrclinonc.2018.19

Savoldo, 2011, CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients, J Clin Invest, 121, 1822, 10.1172/JCI46110

Carpenito, 2009, Control of large, established tumor xenografts with genetically retargeted human T cells containing CD28 and CD137 domains, Proc Natl Acad Sci U S A, 106, 3360, 10.1073/pnas.0813101106

Alabanza, 2017, Function of novel anti-CD19 chimeric antigen receptors with human variable regions is affected by Hinge and transmembrane domains, Mol Ther, 25, 2452, 10.1016/j.ymthe.2017.07.013

Brudno, 2018, Clinical anti-lymphoma activity and toxicity of T cells expressing a novel anti-CD19 chimeric antigen receptor with fully-human variable regions

Fry, 2018, CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy, Nat Med, 24, 20, 10.1038/nm.4441

Jac, 2017, Durable clinical responses in heavily pretreated patients with relapsed/refractory multiple myeloma: Updated results from a multicenter study of bb2121 anti-BCMA CAR T-cell therapy

Pennell, 2018, Human CD19-targeted mouse T cells induce B cell aplasia and toxicity in human CD19 Transgenic mice, Mol Ther, 26, 1423, 10.1016/j.ymthe.2018.04.006

Norelli, 2018, Monocyte-derived IL-1 and IL-6 are differentially required for cytokine-release syndrome and neurotoxicity due to CAR T cells, Nat Med, 24, 739, 10.1038/s41591-018-0036-4

Giavridis, 2018, CAR T cell-induced cytokine release syndrome is mediated by macrophages and abated by IL-1 blockade, Nat Med, 24, 731, 10.1038/s41591-018-0041-7

Taraseviciute, 2018, Chimeric antigen receptor T cell-mediated neurotoxicity in nonhuman primates, Cancer Discov, 8, 750, 10.1158/2159-8290.CD-17-1368

Shalabi, 2018, Systematic evaluation of neurotoxicity in children and young adults undergoing CD22 chimeric antigen receptor T-cell therapy, J Immunother, 41, 350, 10.1097/CJI.0000000000000241

Le, 2018, FDA approval summary: Tocilizumab for treatment of chimeric antigen receptor T cell-induced severe or life-threatening cytokine release syndrome, Oncologist, 23, 943, 10.1634/theoncologist.2018-0028

Shetty, 2014, Tocilizumab in the treatment of rheumatoid arthritis and beyond, Drug Des Devel Ther, 8, 349

Gardner, 2016, Decreased rates of severe CRS seen with early intervention strategies for CD19 CAR-T cell toxicity management, Blood, 128, 586, 10.1182/blood.V128.22.586.586

Singh, 2017, Monocyte lineage-derived IL-6 does not affect chimeric antigen receptor T-cell function, Cytotherapy, 19, 867, 10.1016/j.jcyt.2017.04.001

Nellan, 2018, Improved CNS exposure to tocilizumab after cerebrospinal fluid compared to intravenous administration in rhesus macaques, Blood, 132, 662, 10.1182/blood-2018-05-846428

Paszkiewicz, 2016, Targeted antibody-mediated depletion of murine CD19 CAR T cells permanently reverses B cell aplasia, J Clin Invest, 126, 4262, 10.1172/JCI84813

Gargett, 2014, The inducible caspase-9 suicide gene system as a "safety switch" to limit on-target, off-tumor toxicities of chimeric antigen receptor T cells, Front Pharmacol, 5, 235, 10.3389/fphar.2014.00235

Zhou, 2015, Inducible caspase-9 suicide gene controls adverse effects from alloreplete T cells after haploidentical stem cell transplantation, Blood, 125, 4103, 10.1182/blood-2015-02-628354

Jones, 2014, Improving the safety of cell therapy products by suicide gene transfer, Front Pharmacol, 5, 254, 10.3389/fphar.2014.00254

Drent, 2016, Pre-clinical evaluation of CD38 chimeric antigen receptor engineered T cells for the treatment of multiple myeloma, Haematologica, 101, 616, 10.3324/haematol.2015.137620

Hoyos, 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, 10.1038/leu.2010.75

Wang, 2011, A transgene-encoded cell surface polypeptide for selection, in vivo tracking, and ablation of engineered cells, Blood, 118, 1255, 10.1182/blood-2011-02-337360

Minagawa, 2016, In vitro pre-clinical validation of suicide gene modified anti-CD33 redirected chimeric antigen receptor T-cells for acute myeloid leukemia, PLoS One, 11, 10.1371/journal.pone.0166891

Maus, 2016, Making better chimeric antigen receptors for adoptive T-cell therapy, Clin Cancer Res, 22, 1875, 10.1158/1078-0432.CCR-15-1433

Beatty, 2014, Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce anti-tumor activity in solid malignancies, Cancer Immunol Res, 2, 112, 10.1158/2326-6066.CIR-13-0170