Elotuzumab enhances the anti-tumor activity of Vγ9Vδ2 T cells against primary effusion lymphoma.

Primary Effusion Lymphoma (PEL) is an aggressive B-cell lymphoma with no standard treatment. Vγ9Vδ2 T cells contribute to tumor eradication but have limited cytotoxicity on their own. Elotuzumab (Elo), an anti-SLAMF7 monoclonal antibody approved for multiple myeloma, primarily acts through NK cells; however, its direct effect on γδ T cells has not been reported. In this study, we examined whether Elo enhances γδ T cell cytotoxicity against PEL. We found that SLAMF7 is expressed on both PEL cells and γδ T cells. Elo treatment significantly increased γδ T cell cytotoxicity and degranulation, and these effects were prevented by Fc receptor blockade or by Fc-deficient Elo, indicating an antibody-dependent cellular cytotoxicity (ADCC) mechanism. Our findings demonstrate for the first time that Elo directly boosts γδ T cell anti-tumor activity against PEL, offering novel preclinical evidence for combining Elo with γδ T cell therapy as a potential treatment strategy for this intractable lymphoma.