Anti-BCMA CAR T Cell Development Continues to Evolve for Multiple Myeloma

Each of the many BCMA-targeted chimeric antigen receptor (CAR) T cells in development demonstrate a different efficacy and safety profile, and each have different constructs. None of the agents have reached the FDA yet, but data for many of the agents were presented at the 2018 ASH Annual Meeting.

Showing promising data in the phase I CRB-401 trial, bb2121 is at the front of the race for BCMA development.1 Additionally, LCAR-B38M, has also shown strong phase I results.2 A number of oral abstract sessions at the ASH meeting highlighted other therapies, including MCARH171,3 JCARH125,4 P-BCMA-101,5 FCARH143,6 bb21217,7 CT053,8 and a yet unnamed therapy from HRAIN Biotechnology in China (BCMA-CART).9

Proliferation of CAR T cell Candidates

Four agents currently being explored in the United States provide a look at findings across different CAR T cell constructs, these agents are MCARH171, JCARH125, FCARH143, and P-BCMA-101.

MCARH171 is transduced with a retrovirus, with no predefined CD4:CD8 ratio. The treatment has a CD8 alpha hinge and a 4-1BB costimulatory domain.3 JCARH125 and FCARH143 are similar, as both agents are manufactured from cells with a predefined CD4:CD8 ratio, both have 4-1BB costimulatory domains and fully human BCMA single-chain variable fragment (scFv), and both are transduced with a lentivirus vector.4,6

P-BCMA-101 is manufactured using the piggyback approach, which is a non-viral system for DNA delivery.5 The agent uses a small human fibronectin domain for BCMA. In preclinical work, the design of the molecule resulted in higher T stem cell memory T cells (TSCM), according to senior investigator Krina Patel, MD MSc. “We believe TSCM cells in this product are the key to increase duration of response and reduce toxicity,” she said.

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