Allogeneic V Gamma 9v Delta 2 T-Cell Immunotherapy Exhibits Promising Clinical Safety And Prolongs The Survival Of Patients With Late-Stage Lung Or Liver Cancer

V gamma 9V delta 2 T cells are promising candidates for cellular tumor immunotherapy. Due to their HLA-independent mode of action, allogeneic V gamma 9V delta 2 T cells can be considered for clinical application. To apply allogeneic V gamma 9V delta 2 T cells in adoptive immunotherapy, the methodology used to obtain adequate cell numbers with optimal effector function in vitro needs to be optimized, and clinical safety and efficacy also need to be proven. Therefore, we developed a novel formula to improve the expansion of peripheral gamma delta T cells from healthy donors. Then, we used a humanized mouse model to validate the therapeutic efficacy of expanded gamma delta T cells in vivo; furthermore, the expanded gamma delta T cells were adoptively transferred into late-stage liver and lung cancer patients. We found that the expanded cells possessed significantly improved immune effector functions, including proliferation, differentiation, and cancer cell killing, both in vitro and in the humanized mouse model. Furthermore, a phase I clinical trial in 132 late-stage cancer patients with a total of 414 cell infusions unequivocally validated the clinical safety of allogeneic V gamma 9V delta 2 T cells. Among these 132 patients, 8 liver cancer patients and 10 lung cancer patients who received >= 5 cell infusions showed greatly prolonged survival, which preliminarily verified the efficacy of allogeneic V gamma 9V delta 2 T-cell therapy. Our clinical studies underscore the safety and efficacy of allogeneic V gamma 9V delta 2 T-cell immunotherapy, which will inspire further clinical investigations and eventually benefit cancer patients.