The various physiologic and manipulated antileukemic cytotoxic mechanisms of γδ T cells. (1) Vγ9Vδ2 T cells recognize blasts via the CD277/IPP/rhoB axis,34 and (2) CD1 ligands are recognized by Vδ1 γδ T cells.78 (3) Stress-induced self-ligands (MICA/B, ULBPs) are recognized by NKG2D15 ; (4) human leukocyte B–associated transcript 3 is recognized by natural cytotoxicity receptors NKp3018 ; (5) nectin-2 (CD112) and poliovirus receptor (CD155) are the ligands for DNAM-119,20 ; and (6) therapeutic monoclonal antibodies can induce antibody-dependent cellular cytotoxicity via the Fc receptor III.39 (7) Bispecific antibodies can activate γδ T cells via anti-Vγ9 single chain Fv,98 and (8) γδ T cells can be redirected using CARs86 or (9) through the transduction of an exogenous αβ TCR directed against a tumor-associated antigen.89 (10) The transfer of a Vγ9Vδ2 TCR recognizing blasts via the CD277/IPP/rhoB axis with optimum affinity for the target into αβ T cells also confers appropriate help through engineered CD4 T cells.92 FcR, Fc receptor III; TAA, tumor-associated antigen.
