Tang Y, Liu W, Kadu S, et al. Exploiting the CD200-CD200R Immune Checkpoint Axis in Multiple Myeloma to Enhance CAR-T Therapy. Blood. 2023; (doi: 10.1182/blood.2022018658).
New findings reinforce the critical role of a CD200R-CD28 switch in chimeric antigen receptor (CAR) T-cell therapy for multiple myeloma (MM), with the resulting costimulation overcoming previous treatment shortcomings. In MM, overexpression of the immune checkpoint CD200 on aberrant plasma cells undermines the activity of CAR-T cells. Researchers experimented with different tactics to avoid this CD200-mediated immune suppression, including CD200 receptor (CD200R) knockout and CD200R non-signaling approaches. The former proved to have a negative effect, while the latter induced only modest benefits. Another option — which leveraged the CD200 signal to generate CD28 costimulation — proved to be the superior strategy for improving CAR-T function in CD200+ MM models. The CD200R-CD28 switch improved cytotoxicity, proliferation, and CAR-T cell metabolism, as validated in mouse xenograft models of plasmacytoma and disseminated bone marrow predominant disease.