Allogeneic Anti-BCMA CAR T Cells Are Superior to Multiple Myeloma-derived CAR T Cells in Preclinical Studies and May Be Combined with Gamma Secretase Inhibitors.

Multiple myeloma remains an incurable plasma cell malignancy despite the rapidly evolving treatment landscape. Chimeric antigen receptor T cells targeted against BCMA have recently shown great promise in relapsed refractory multiple myeloma; however, all patients ultimately still progress from their disease. Lack of CAR T-cell persistence, impaired T-cell fitness in autologous CAR T-cell products and the presence of an immunosuppressive bone marrow (BM) microenvironment are contributory factors to treatment failure. We generated anti-BCMA CAR T cells from healthy donors (HD) and patients with multiple myeloma at different stages of disease to compare their T-cell profile, fitness, and cytotoxic activity in preclinical studies. We also used an Multiple myeloma is an incurable cancer of the plasma cells. A new therapy with anti-BCMA CAR T cells - the patient's own T cells genetically engineered to find and kill myeloma cancer cells - has shown encouraging results. Unfortunately, patients still relapse. In this study, we propose to use T cells from HD volunteers, which have a stronger T-cell fitness, higher cancer killing capacity, and are ready to be administered when needed.

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© 2022 The Authors; Published by the American Association for Cancer Research.

Déclaration de conflit d'intérêts

A.M. Metelo reports grants from Allogene Therapeutics during the conduct of the study. A. Jozwik reports grants from Allogene during the conduct of the study and grants from Servier outside the submitted work. C. Graham reports grants from Allogene during the conduct of the study; grants from Servier outside the submitted work. M. Streetly reports personal fees from Bristol Myers Squibb / Celgene, personal fees from Janssen-Cilag, and personal fees from EuSa Pharma outside the submitted work. T. Bentley reports non-financial support and other from Allogene Therapeutics, Inc during the conduct of the study. B. Boldajipour reports personal fees from Pfizer, personal fees from Kite Pharma, and personal fees from Lyell Immunopharma outside the submitted work; in addition, B. Boldajipour has a patent to US10294304B2 issued. C. Sommer reports other from Allogene Therapeutics, Inc. outside the submitted work; in addition, C. Sommer has a patent to US Provisional Application Nos.: 62/962,014 and 63/117,281 pending. B. Sasu is an employee and receives stocks and salary from Allogene Therapeutics. R. Benjamin reports grants from Allogene Therapeutics during the conduct of the study. No disclosures were reported by the other authors.