摘要
Vγ9Vδ2 T cells are promising candidates for cellular tumor immunotherapy.Due to their HLA-independent mode of action,allogeneic Vγ9Vδ2 T cells can be considered for clinical application.To apply allogeneic Vγ9Vδ2 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 peripheralγδT cells from healthy donors.Then,we used a humanized mouse model to validate the therapeutic efficacy of expandedγδT cells in vivo;furthermore,the expandedγδT 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 Vγ9Vδ2 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 Vγ9Vδ2 T-cell therapy.Our clinical studies underscore the safety and efficacy of allogeneic Vγ9Vδ2 T-cell immunotherapy,which will inspire further clinical investigations and eventually benefit cancer patients.
基金
This work was supported by the Key Program of the National Natural Science Foundation of China(31830021)
Major International Joint Research Program of China(31420103901)
“111 project”(B16021)
Scientific and Technological Plan of Guangdong Province(201704KW010)(Z.Y.)
Fundamental Research Funds for the Central Universities,Natural Science Foundation of Guangdong Province,China(2020A1515010132)(Y.W.)
General Research Fund,Research Grants Council of Hong Kong(17122519,17121214,17115015,and 17126317)(W.T.)
Hong Kong SAR,China
This work was also partially supported by the National Natural Science Foundation of China(31570898)
the Natural Science Foundation of Guangdong Province,China(2016A030313112)(Z.X.)
grant Ka 502/19-1 from the German Research Council(Deutsche Forschungsgemeinschaft)
the Cluster of Excellence ExC 306“Inflammation-at-Interfaces”(Deutsche Forschungsgemeinschaft)(D.K.)
Y.H.was supported by the China Postdoctoral Science Foundation(2017M622898)
Y.X.was supported by the Postdoctoral Fund of the First Affiliated Hospital of Jinan University(809008)
L.K.was supported by a long-term fellowship from the German Academic Exchange Service(DAAD)
C.P.is the recipient of a grant from the Erich und Gertrud Roggenbruck Foundation.
