TRAC-integrated CD28 wild-type CD3ζ BCMA CAR-T

TRAC-integrated CD28 wild-type CD3ζ BCMA CAR-T is an investigational chimeric antigen receptor (CAR) T-cell therapy designed to treat multiple myeloma by targeting the B-cell maturation antigen (BCMA). This construct is engineered using CRISPR/Cas9 technology to integrate the CAR transgene specifically into the T-cell receptor alpha constant (TRAC) locus. This site-specific integration results in the knockout of the endogenous T-cell receptor, potentially reducing the risk of graft-versus-host disease (GvHD) and ensuring uniform CAR expression under the endogenous TRAC promoter. The CAR architecture includes a BCMA-binding single-chain variable fragment (scFv) derived from the bb2121 clone, a CD28 costimulatory domain, and a wild-type CD3ζ signaling domain. In preclinical studies, this wild-type version demonstrated significant anti-tumor activity but was used primarily as a benchmark to evaluate the enhanced persistence and efficacy of next-generation signaling domains, such as the 1XX-modified CD3ζ.

Other names

TRAC-BCMA-CD28-CD3ζ CAR-TTRAC-targeted BCMA CAR-T (wild-type)