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AACR 2022: Can Novel CAR T Cells Overcome BCMA Antigen Loss in Myeloma?

By: Sarah Campen, PharmD
Posted: Wednesday, April 13, 2022

Although anti–B-cell maturation antigen (anti-BCMA) chimeric antigen receptor (CAR) T cells have had clinical success in the treatment of multiple myeloma, patient outcomes suggest that targeting BCMA alone may not be sufficient. Researchers have developed a novel antibody against a second target—transmembrane activator and CAML interactor (TACI)—as a potential treatment option for multiple myeloma. According to Marcela V. Maus, MD, PhD, of Massachusetts General Hospital, Boston, and colleagues, this antibody specifically recognizes TACI-positive cells and has no recognition of non–B-cell peripheral blood mononuclear cells. Their findings were presented at the American Association for Cancer Research (AACR) Annual Meeting 2022 (Abstract 556/10).

The study authors developed second-generation CAR T cells using the single-chain variable fragment from this antibody. The anti-TACI CARs were cytotoxic in vitro at comparable levels to anti-BCMA CARs against multiple myeloma cell lines MM1S and RPMI-8226. They also created BCMA-knockout MM1S cells; although mice treated with anti-BCMA CARs had outgrowth of tumor, those treated with anti-TACI CARs retained antitumor activity.

To overcome potential antigen loss of either BCMA or TACI, Dr. Maus and colleagues designed tandem bispecific CAR T cells based on both single-targeted CAR designs. These BCMA and TACI dual-targeting CARs appeared to be functional in vitro and in vivo, even in the context of single antigen loss. “Our studies provide a potential superior therapeutic option that remains efficacious in the context of BCMA antigen loss,” concluded the study authors.

Disclosure: For full disclosures of the study authors, visit

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