MM3 CAR T

MM3 CAR T is an experimental chimeric antigen receptor (CAR) T-cell therapy designed to treat multiple myeloma and other plasma cell dyscrasias. Unlike conventional CAR-T therapies that use single-chain variable fragments (scFvs) derived from mammalian antibodies, MM3 CAR T utilizes a variable lymphocyte receptor (VLR) binding domain. VLRs are antibody analogs found in jawless vertebrates like lampreys. The MM3 VLR specifically recognizes a unique epitope formed by the dimerization of CD38, which is highly specific to human plasma cells and plasmablasts. This targeting strategy aims to overcome the limitations of standard CD38-directed therapies, which often face off-tumor toxicity due to the broad expression of CD38 on various immune cell lineages. The CAR construct incorporates a CD8 hinge and transmembrane domain, along with 4-1BB and CD3zeta intracellular signaling domains. Preclinical studies have demonstrated specific activation and killing of CD38-dimer-positive cell lines and effective homing in xenograft models.