MGDL-CD828Z

MGDL-CD828Z is an experimental chimeric antigen receptor (CAR) T-cell therapy developed by researchers at the National Cancer Institute (NCI) to target the constant region of the gamma-delta (γδ) T-cell receptor (TCR). The construct is composed of the MGDL single-chain variable fragment (scFv), which recognizes a constant region shared by all γδ TCRs, a CD8α hinge and transmembrane domain, a CD28 costimulatory domain, and a CD3ζ activation domain. It is being investigated for the treatment of aggressive γδ T-cell malignancies, including hepatosplenic T-cell lymphoma and T-cell acute lymphoblastic leukemia, as well as potential applications in autoimmune diseases. In preclinical studies, MGDL-CD828Z demonstrated antigen-specific activation, cytokine release, and cytotoxicity against γδ TCR-expressing cell lines such as Loucy, MOLT13, and BE13, although comparative studies indicated that related constructs utilizing a CD28 hinge and transmembrane domain (MGDL-28Z) may offer enhanced cytokine production.