MGDL-CD8BBZ

MGDL-CD8BBZ is an experimental chimeric antigen receptor (CAR) T-cell therapy developed by researchers at the National Cancer Institute (NCI). It specifically targets the constant region of the gamma-delta (γδ) T-cell receptor (TCR), which is expressed on the surface of γδ T-cell malignancies such as hepatosplenic T-cell lymphoma and certain cases of T-cell acute lymphoblastic leukemia (T-ALL). The CAR construct consists of a single-chain variable fragment (scFv) designated MGDL, a CD8α hinge and transmembrane domain, a 4-1BB (CD137) costimulatory domain, and a CD3ζ signaling domain. In preclinical studies, MGDL-CD8BBZ demonstrated antigen-specific activation and cytotoxicity against γδ TCR-expressing cell lines (Loucy, MOLT13, BE13), although it showed lower in vitro proliferation compared to CD28-containing variants. It is also being explored for potential applications in autoimmune diseases where γδ T cells play a pathogenic role.