Overview of anti-BCMA CAR-T immunotherapy for multiple myeloma and relapsed/refractory multiple myeloma.
anti-BCMA CAR-T immunotherapy
chimeric antigen receptor T
multiple myeloma
Journal
Scandinavian journal of immunology
ISSN: 1365-3083
Titre abrégé: Scand J Immunol
Pays: England
ID NLM: 0323767
Informations de publication
Date de publication:
Aug 2020
Aug 2020
Historique:
received:
24
12
2019
revised:
23
03
2020
accepted:
19
05
2020
pubmed:
30
5
2020
medline:
31
7
2020
entrez:
30
5
2020
Statut:
ppublish
Résumé
Multiple myeloma (MM) is a haematological malignancy caused by malignant proliferation of plasma cells in bone marrow. In recent years, MM patients are commonly treated with chemotherapy, autologous stem cell transplantation, protease inhibitors, immunomodulatory drugs and monoclonal antibodies, however most patients eventually relapse. Therefore, more effective therapies are highly needed. Anti-BCMA CAR-T therapy, a novel and efficacious method for treating MM and relapsed/refractory multiple myeloma (RRMM), has been designed and applied in clinics. The CAR-T can specifically recognize the targeted molecule B cell maturation antigen (BCMA) and kill MM cells expressing BCMA and several clinical trials have revealed high response rates in the therapy. Herein, we summarize the developments, the current design and clinical trials, the side effects of anti-BCMA CAR-T therapy and comparison of it with other CAR-T therapies.
Substances chimiques
B-Cell Maturation Antigen
0
Receptors, Chimeric Antigen
0
TNFRSF17 protein, human
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12910Subventions
Organisme : National Natural Science Foundation of China
ID : 81273308
Informations de copyright
© 2020 The Scandinavian Foundation for Immunology.
Références
Filley AC, Henriquez M, Dey M. CART immunotherapy: development success, and translation to malignant Gliomas and Other Solid Tumors. Front. Oncol. 2018;8:453.
Pampusch MS, Haran KP, Hart GT, et al. Rapid transduction and expansion of transduced t cells with maintenance of central memory populations. Mol Ther Methods Clin Dev. 2020;16:1-10.
Mehta GR, Suhail F, Haddad RY, Zalzaleh G, Lerma EV. Multiple myeloma. Dis Mon. 2014;60:483-488.
Smith EL, Mailankody S, Staehr M, et al. BCMA-targeted CAR T-cell therapy plus radiotherapy for the treatment of refractory myeloma reveals potential synergy. Cancer Immunol Res. 2019;7:1047-1053.
Hartmann J, Schussler-Lenz M, Bondanza A, Buchholz CJ. Clinical development of CAR T cells-challenges and opportunities in translating innovative treatment concepts. EMBO Mol Med. 2017;9:1183-1197.
Ormhoj M, Bedoya F, Frigault MJ, Maus MV. CARs in the lead against multiple myeloma. Curr Hematol Malig Rep. 2017;12:119-125.
Wang ZG, Wu ZQ, Liu Y, Han WD. New development in CAR-T cell therapy. J Hematol Oncol. 2017;10:53.
Ma TT, Shi J, Liu HS. Chimeric antigen receptor T cell targeting B cell maturation antigen immunotherapy is promising for multiple myeloma. Ann. Hematol. 2019;98:813-822.
Wang LY, Yao RX, Zhang LF, Fan CB, Ma LN, Liu J. Chimeric antigen receptor T cell therapy and other therapeutics for malignancies: combination and opportunity. Int Immunopharmacol. 2019;70:498-503.
Gomes-Silva D, Ramos CA. Cancer immunotherapy using CAR-T cells: from the research bench to the assembly line. Biotechnol. J. 2018;13:1700097.
Schwarzbich MA, Witzens-Harig M. Cellular immunotherapy in B-cell malignancy. Oncol Res Treatment. 2017;40:674-681.
Zhang C, Liu J, Zhong JF, Zhang X. Engineering CAR-T cells. Biomarker Res. 2017;5:22.
Hay KA, Turtle CJ. Chimeric Antigen Receptor (CAR) T cells: lessons learned from targeting of CD19 in B-cell malignancies. Drugs. 2017;77:237-245.
Mato AR, Thompson MC, Nabhan C, Svoboda J, Schuster SJ. Chimeric antigen receptor T-cell therapy for chronic lymphocytic leukemia: a narrative review. Clin Lymphoma Myeloma Leuk. 2017;17:852-856.
Xia AL, Wang XC, Lu YJ, Lu XJ, Sun BC. Chimeric-antigen receptor T (CAR-T) cell therapy for solid tumors: challenges and opportunities. Oncotarget. 2017;8:90521-90531.
Coquery CM, Erickson LD. Regulatory roles of the tumor necrosis factor receptor BCMA. Crit Rev Immunol. 2012;32:287-305.
Ghosh A, Mailankody S, Giralt SA, Landgren CO, Smith EL, Brentjens RJ. CAR T cell therapy for multiple myeloma: where are we now and where are we headed? Leuk Lymphoma. 2018;59:2056-2067.
Kim J, Gross JA, Dillon SR, Min JK, Elkon KB. Increased BCMA expression in lupus marks activated B cells, and BCMA receptor engagement enhances the response to TLR9 stimulation. Autoimmunity. 2011;44:69-81.
Carpenter RO, Evbuomwan MO, Pittaluga S, et al. B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma. Clin Cancer Res. 2013;19:2048-2060.
Martinez-Cingolani C, Bories JC. Development of chimeric antigen receptors for multiple myeloma. Biochem Soc Trans. 2016;44:397-405.
Maus MV, June CH. Zoom Zoom: racing CARs for multiple myeloma. Clin Cancer Res. 2013;19:1917-1919.
Berahovich R, Zhou H, Xu S, et al. Cells based on novel BCMA monoclonal antibody block multiple myeloma cell growth. Cancers (Basel). 2018;10:323.
Salazar-Camarena DC, Ortiz-Lazareno PC, Cruz A, et al. Association of BAFF, APRIL serum levels, BAFF-R, TACI and BCMA expression on peripheral B-cell subsets with clinical manifestations in systemic lupus erythematosus. LUPUS. 2016;25:582-592.
Sanchez E, Tanenbaum EJ, Patil S, et al. The clinical significance of B-cell maturation antigen as a therapeutic target and biomarker. Expert Rev Mol Diagn. 2018;18:319-329.
Ali SA, Shi V, Maric I, et al. T cells expressing an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of multiple myeloma. Blood. 2016;128:1688-1700.
Friedman KM, Garrett TE, Evans JW, et al. Effective targeting of multiple B-cell maturation antigen-expressing hematological malignances by anti-B-cell maturation antigen chimeric antigen receptor T cells. Hum Gene Ther. 2018;29:585-601.
Raje N, Berdeja J, Lin Y, et al. Anti-BCMA CAR T-cell therapy bb2121 in relapsed or refractory multiple myeloma. New Engl J Med. 2019;380:1726-1737.
Adams GB, Feng J, Ghogha A, et al. Development of KITE-585: a fully human BCMA CAR T-cell therapy for the treatment of multiple myeloma. Cancer Res. 2017;77:4979.
Cornell RF, Locke FL, Bishop MR, et al. A phase 1 multicenter study evaluating KITE-585, an autologous anti-BCMA CAR T-cell therapy, in patients with relapsed/refractory multiple myeloma. J Clin Oncol. 2018;36:TPS3103.
Jiang S, Jin J, Hao S, et al. Low dose of human scFv-derived BCMA-targeted CAR-T cells achieved fast response and high complete remission in patients with relapsed/refractory multiple myeloma. Blood. 2018;132:960.
Hao S, Jin J, Yu K, et al. CT053, anti-BCMA CAR T-cell therapy for relapsed/refractory multiple myeloma: proof of concept results from a phase I study. Clin Lymphoma Myeloma Leukemia. 2019;19:E54-E55.
Li C, Zhou X, Wang J, et al. Clinical responses and pharmacokinetics of fully human BCMA targeting CAR T cell therapy in relapsed/refractory multiple myeloma. Clin Lymphoma Myeloma Leukemia. 2019;19:E23-E24.
Xu J, Wang Q, Xu H, et al. Anti-BCMA CAR-T cells for treatment of plasma cell dyscrasia: case report on POEMS syndrome and multiple myeloma. J Hematol Oncol. 2018;11:128.
Tai Y-T, Acharya C, An G, et al. APRIL and BCMA promote human multiple myeloma growth and immunosuppression in the bone marrow microenvironment. Blood. 2016;127:3225-3236.
Lee L, Draper B, Chaplin N, et al. An APRIL-based chimeric antigen receptor for dual targeting of BCMA and TACI in multiple myeloma. Blood. 2018;131:746-758.
Schmidts A, Ormhøj M, Choi BD, et al. Rational design of a trimeric APRIL-based CAR-binding domain enables efficient targeting of multiple myeloma. Blood Advances. 2019;3:3248-3260.
Fan X, Zhuang Q, Yang L, et al. Preclinical assessment of LCAR-B38M, a novel BCMA-targeting chimeric antigen receptor (CAR)-T cell therapy in relapsed/refractory multiple myeloma. Clin Lymphoma Myeloma Leukemia. 2019;19:E160.
Zhao WH, Liu J, Wang BY, et al. A phase 1, open-label study of LCAR-B38M, a chimeric antigen receptor T cell therapy directed against B cell maturation antigen, in patients with relapsed or refractory multiple myeloma. J Hematol Oncol. 2018;11:141.
Chen KH, Wada M, Pinz KG, et al. A compound chimeric antigen receptor strategy for targeting multiple myeloma. Leukemia. 2018;32:402-412.
Li C, Mei H, Hu Y, et al. Improved efficacy and safety of a dual-target CAR-T cell therapy targeting BCMA and CD38 for relapsed/refractory multiple myeloma from a phase I study. Eur J Immunol. 2019;49:1723-1724.
Yan Z, Cao J, Cheng H, et al. A combination of humanised anti-CD19 and anti-BCMA CAR T cells in patients with relapsed or refractory multiple myeloma: a single-arm, phase 2 trial. Lancet Haematology. 2019;6:E521-E529.
Pont MJ, Hill T, Cole GO, et al. gamma-Secretase inhibition increases efficacy of BCMA-specific chimeric antigen receptor T cells in multiple myeloma. Blood. 2019;134:1585-1597.
Hermanson D, Barnett BE, Rengarajan S, et al. PiggyBac-manufactured anti-BCMA Centyrin-based CAR-T therapeutic exhibits improved potency and durability. Cancer Res. 2017;77:3759.
Hermanson DL, Barnett BE, Rengarajan S, et al. A novel Bcma-specific, centyrin-based CAR-T product for the treatment of multiple myeloma. Blood. 2016;128:2127.
Mathur R, Barnett BE, Hermanson D, et al. B-cell maturation antigen (BCMA)-pecific, centyrin (TM)-based, PiggyBac (TM)-Transposed CAR-T memory stem cells are effective against p53(-/-) and patient-derived multiple myeloma tumors. Blood. 2017;130:3068.
Gregory T, Cohen AD, Costello CL, et al. Efficacy and safety of P-Bcma-101 CAR-T cells in patients with relapsed/refractory (r/r) multiple myeloma (MM). Blood. 2018;132:1012.
Shah N, Alsina M, Siegel DS, et al. Initial results from a phase 1 clinical study of bb21217, a next-generation anti Bcma CAR T therapy. Blood. 2018;132:488.
Mailankody S, Htut M, Lee KP, et al. JCARH125, anti-BCMA CAR T-cell therapy for relapsed/refractory multiple myeloma: initial proof of concept results from a phase 1/2 multicenter study (EVOLVE). Blood. 2018;132:957.
Liu Y, Chen Z, Fang H, et al. Durable remission achieved from Bcma-directed CAR-T therapy against relapsed or refractory multiple myeloma. Blood. 2018;132:956.
Mailankody S, Ghosh A, Staehr M, et al. Clinical responses and pharmacokinetics of MCARH171, a human-derived bcma targeted CAR T cell therapy in relapsed/refractory multiple myeloma: final results of a phase I clinical trial. Blood. 2018;132:959.
Yao X, Zhu S, Huang J, et al. Developing a novel anti-Bcma CAR-T for relapsed or refractory multiple myeloma. Blood. 2019;134:50.
Lin L, Xing LJ, Acharya CM, et al. CD8+Anti-BCMA mRNA CAR T-cells effectively kill human multiple myeloma cells in vitro and in vivo. Blood. 2017;130:3067.
Lin L, Xing L, Cho S-F, et al. Preclinical evaluation of CD8+Anti-BCMA mRNA CAR T-Cells for control of multiple myeloma. Clin Lymphoma Myeloma Leukemia. 2019;19:E169.
Sommer C, Bentley T, Sutton J, et al. Off-the-shelf AlloCAR T (TM) cells targeting BCMA for the treatment of multiple myeloma. Clin Lymphoma Myeloma Leukemia. 2019;19:E24.
Sommer C, Boldajipour B, Valton J, et al. ALLO-715, an allogeneic BCMA CAR T therapy possessing an off-switch for the treatment of multiple myeloma. Blood. 2018;132:591.
Cranert S, Richter M, Tong M, et al. Robust, reproducible and highly scalable manufacturing of P-BCMA-ALLO1, an allogeneic CAR-T stem cell memory product for multiple myeloma, from numerous healthy donors. J IMMUNOTHER CANCER. 2019;7:P165.
Richter M, Cranert S, Tan YN, et al. P-BCMA-ALLO1-a nonviral, allogeneic anti-BCMA CAR-T therapy with potent antitumor function for the treatment of multiple myeloma. J IMMUNOTHER CANCER. 2019;7:O7.
Wang XX, Barnett BE, Martin C, et al. Production of universal anti-Bcma CAR-T cells with reduced alloreactivity, but potent effector function for the treatment of multiple myeloma. Blood. 2017;130:503.
Abbasi-Kenarsari H, Shafaghat F, Baradaran B, Movassaghpour AA, Shanehbandi D, Kazemi T. Cloning and expression of CD19, a human B-cell marker in NIH-3T3 cell line. Avicenna J Med Biotechnol. 2015;7:39-44.
Fairfax KA, Tsantikos E, Figgett WA, et al. BAFF-driven autoimmunity requires CD19 expression. J Autoimmun. 2015;62:1-10.
Morbach H, Schickel JN, Cunningham-Rundles C, et al. CD19 controls Toll-like receptor 9 responses in human B cells. J Allergy Clin Immunol. 2016;137(889-98):e6.
Garfall AL, Stadtmauer EA, Hwang W-T, et al. Anti-CD19 CAR T cells with high-dose melphalan and autologous stem cell transplantation for refractory multiple myeloma. JCI insight. 2018;3:e120505.
Nerreter T, Letschert S, Götz R, et al. Super-resolution microscopy reveals ultra-low CD19 expression on myeloma cells that triggers elimination by CD19. CAR-T. Nat Commun. 2019;10:3137.
Boudreault JS, Touzeau C, Moreau P. The role of SLAMF7 in multiple myeloma: impact on therapy. Expert Rev Clin Immunol. 2017;13:67-75.
van de Donk NWCJ, Moreau P, Plesner T, et al. Clinical efficacy and management of monoclonal antibodies targeting CD38 and SLAMF7 in multiple myeloma. Blood. 2016;127:681-695.
Danhof S, Gogishvili T, Koch S, et al. CAR-engineered T cells specific for the Elotuzumab target SLAMF7 eliminate primary myeloma cells and confer selective fratricide of SLAMF7+normal lymphocyte subsets. Blood. 2015;126:115.
Gogishvili T, Danhof S, Prommersberger S, et al. SLAMF7-CAR T cells eliminate myeloma and confer selective fratricide of SLAMF7(+) normal lymphocytes. Blood. 2017;130:2838-2847.
Huang H, Wu HW, Hu YX. Current advances in chimeric antigen receptor T-cell therapy for refractory/relapsed multiple myeloma. J Zhejiang Univ Sci B. 2020;21:29-41.
Ishibashi M, Tamura H, Asayama T, et al. The new immunoreceptor SLAMF3 promotes aggressive biological and clinical characteristics in multiple myeloma. Blood. 2017;130:3055.
Radhakrishnan SV, Luetkens T, Scherer SD, et al. CD229 CAR T cells eliminate multiple myeloma and tumor propagating cells without fratricide. Nat Commun. 2020;11:798.
Radhakrishnan SV, Luetkens T, Yousef S, et al. Chimeric Antigen Receptor (CAR) T cells specific for CD229: a potentially curative approach for multiple myeloma. Blood. 2017;130:3142.
Danylesko I, Beider K, Shimoni A, Nagler A. Novel strategies for immunotherapy in multiple myeloma: previous experience and future directions. Clin Dev Immunol. 2012;2012:753407.
Mikkilineni L, Kochenderfer JN. Chimeric antigen receptor T-cell therapies for multiple myeloma. Blood. 2017;130:2594-2602.
Chung C. Role of immunotherapy in targeting the bone marrow microenvironment in multiple myeloma: an evolving therapeutic strategy. Pharmacotherapy. 2017;37:129-143.
Bonello F, D'Agostino M, Moscvin M, Cerrato C, Boccadoro M, Gay F. CD38 as an immunotherapeutic target in multiple myeloma. Expert Opin Biol Ther. 2018;18:1209-1221.
Kriegsmann K, Kriegsmann M, Cremer M, et al. Cell-based immunotherapy approaches for multiple myeloma. Br J Cancer. 2019;120:38-44.
Morandi F, Horenstein AL, Costa F, Giuliani N, Pistoia V, Malavasi F. CD38: a target for immunotherapeutic approaches in multiple myeloma. Fronts Immunol. 2018;9:2722.
Shah UA, Mailankody S. CAR T and CAR NK cells in multiple myeloma: expanding the targets. Best Pract Res Clin Haematol. 2020;33:101141.
Chen D, Zou JX, Zong YH, Meng HM, An GL, Yang L. Anti-human CD138 monoclonal antibodies and their bispecific formats: generation and characterization. Immunopharmacol. Immunotoxicol. 2016;38:175-183.
Gharbaran R. Advances in the molecular functions of syndecan-1 (SDC1/CD138) in the pathogenesis of malignancies. Crit Rev Oncol Hematol. 2015;94:1-17.
Teng YH, Aquino RS, Park PW. Molecular functions of syndecan-1 in disease. Matrix Biol. 2012;31:3-16.
Jiang H, Zhang W, Shang P, et al. Transfection of chimeric anti-CD138 gene enhances natural killer cell activation and killing of multiple myeloma cells. Mol Oncol. 2014;8:297-310.
McCarron MJ, Park PW, Fooksman DR. CD138 mediates selection of mature plasma cells by regulating their survival. Blood. 2017;129:2749-2759.
Guo BO, Chen M, Han Q, et al. CD138-directed adoptive immunotherapy of chimeric antigen receptor (CAR)-modified T cells for multiple myeloma. J Cell Immunother. 2016;2:28-35.
Atamaniuk J, Gleiss A, Porpaczy E, et al. Overexpression of G protein-coupled receptor 5D in the bone marrow is associated with poor prognosis in patients with multiple myeloma. Eur J Clin Invest. 2012;42:953-960.
Smith EL, Harrington K, Staehr M, et al. GPRC5D is a target for the immunotherapy of multiple myeloma with rationally designed CAR T cells. Sci Transl Med. 2019;11:eaau7746.
Gprc5d car T-cell therapy has antitumor activity in multiple myeloma. Cancer Discov. 2019;9:690.
Murad JM, Baumeister SH, Werner L, et al. Manufacturing development and clinical production of NKG2D chimeric antigen receptor-expressing T cells for autologous adoptive cell therapy. Cytotherapy. 2018;20:952-963.
Serna J, Valeri A, Gobelli DJ, et al. New gene-editing strategy for allogeneic NKG2D-CAR T cell production. Hum Gene Ther. 2019;30:A49.
Lee YS, Heo W, Nam J, Jeung YH, Bae J. The combination of ionizing radiation and proteasomal inhibition by bortezomib enhances the expression of NKG2D ligands in multiple myeloma cells. J Radiat Res. 2018;59:245-252.
Baumeister SH, Murad J, Werner L, et al. Phase I trial of autologous CAR T cells targeting NKG2D ligands in patients with AML/MDS and multiple myeloma. Cancer Immunol Res. 2019;7:100-112.
Casucci M, Nicolis di Robilant B, Falcone L, et al. CD44v6-targeted T cells mediate potent antitumor effects against acute myeloid leukemia and multiple myeloma. Blood. 2013;122:3461-3472.
Casucci M, Nicolis di Robilant B, Falcone L, et al. Off-tumor target expression levels do not predict CAR-T cell killing: a foundation for the safety of CD44v6-targeted T cells. Blood. 2013;122:142.
Carrabba MG, Casucci M, Hudecek M, et al. Phase I-IIa clinical trial to assess safety and efficacy of MLM-CAR44.1, a CD44v6 directed CAR-T in relapsed/refractory acute myeloid leukemia (AML) and multiple myeloma (MM). Blood. 2018;132:5790.
Vera J, Savoldo B, Vigouroux S, et al. T lymphocytes redirected against the kappa light chain of human immunoglobulin efficiently kill mature B lymphocyte-derived malignant cells. Blood. 2006;108:3890-3897.
Ramos CA, Savoldo B, Torrano V, et al. Clinical responses with T lymphocytes targeting malignancy-associated kappa light chains. J Clin Invest. 2016;126:2588-2596.
Neelapu SS. Managing the toxicities of CAR T-cell therapy. Hematol Oncol. 2019;37:48-52.
Brudno JN, Kochenderfer JN. Recent advances in CAR T-cell toxicity: mechanisms, manifestations and management. Blood Rev. 2019;34:45-55.
Xu J, Chen LJ, Yang SS, et al. Exploratory trial of a biepitopic CAR T-targeting B cell maturation antigen in relapsed/refractory multiple myeloma. Proc Natl Acad Sci USA. 2019;116:9543-9551.
Danhof S, Hudecek M, Smith EL. CARs and other T cell therapies for MM: the clinical experience. Best Pract Res Clin Haematol. 2018;31:147-157.
Cohen AD. CAR T cells and other cellular therapies for multiple myeloma: 2018 update. Am Soc Clin Oncol Educ Book. 2018;38:e6-e15.
Garfall AL, Lancaster E, Stadtmauer EA, et al. Posterior Reversible Encephalopathy Syndrome (PRES) after infusion of anti-Bcma CAR T Cells (CART-BCMA) for multiple myeloma: successful treatment with cyclophosphamide. Blood. 2016;128:5702.
Madduri D, Dhodapkar MV, Lonial S, Jagannath S, Cho HJ. SOHO state of the art updates and next questions: T-cell-directed immune therapies for multiple myeloma: chimeric antigen receptor-modified T cells and bispecific T-cell-engaging agents. Clin Lymphoma Myeloma Leuk. 2019;19:537-544.
Tai Y-T, Mayes PA, Acharya C, et al. Novel anti-B-cell maturation antigen antibody-drug conjugate (GSK2857916) selectively induces killing of multiple myeloma. Blood. 2014;123:3128-3138.
Cho SF, Anderson KC, Tai YT. Targeting B Cell Maturation Antigen (BCMA) in multiple myeloma: potential uses of BCMA-based immunotherapy. Front Immunol. 2018;9:1821.
Giuliani N, Accardi F, Marchica V, et al. Novel targets for the treatment of relapsing multiple myeloma. Expert Rev Hematol. 2019;12:481-496.
Gavriatopoulou M, Ntanasis-Stathopoulos I, Dimopoulos MA, Terpos E. Anti-BCMA antibodies in the future management of multiple myeloma. Expert Rev Anticancer Ther. 2019;19:319-326.
Gantke T, Reusch U, Ellwanger K, Fucek I, Weichel M, Treder M. AFM26-A novel CD16A-directed bispecific TandAb targeting BCMA for multiple myeloma. Cancer Res. 2017;77:5671.
Hipp S, Tai Y-T, Blanset D, et al. A novel BCMA/CD3 bispecific T-cell engager for the treatment of multiple myeloma induces selective lysis in vitro and in vivo. Leukemia. 2017;31:1743-1751.
Tai YT, Anderson KC. B cell maturation antigen (BCMA)-based immunotherapy for multiple myeloma. Expert Opin Biol Ther. 2019;19:1143-1156.