Genetic engineering and allogeneic optimization of Vδ1 γδ CAR-T cells (ADI-270) for cancer immunotherapy

Genetic engineering has fundamentally transformed T cell-based therapies by enabling tumor targeting capability, improving their functionality, and facilitating allogeneic use. These strategies-originally developed in αβ chimeric antigen receptor (CAR)-T cells-have become increasingly established as blueprints for enhancing the function of other immune effector cells, including gamma delta (γδ) T cells. A recent study by Nishimoto et al showcased the adaptation of these engineering approaches to Vδ1 γδ T cells (ADI-270) by coexpressing a CD70-targeted CAR and a dominant-negative TGFβRII receptor (dnTGFβRII) to target CD70⁺ malignancies, addressing immunosuppression and host-versus-graft rejection. This commentary explores αβ T cell-derived engineering strategies applicable to γδ T cells, while also highlighting genome-editing innovations poised to advance next-generation γδ CAR-T development.