Allogeneic Vγ9Vδ2 T-cell immunotherapy exhibits promising clinical safety and prolongs the survival of patients with late-stage lung or liver cancer.

Autor: Xu Y; The First Affiliated Hospital, Faculty of Medical Science, Jinan University, Guangzhou, 510632, Guangdong, PR China.; Zhuhai Precision Medical Center, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Jinan University, Zhuhai, 519000, Guangdong, PR China.; The Biomedical Translational Research Institute, Jinan University, Guangzhou, 510632, Guangdong, PR China., Xiang Z; Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, PR China., Alnaggar M; The Biomedical Translational Research Institute, Jinan University, Guangzhou, 510632, Guangdong, PR China.; Tongji Chibi Hospital, Tongji Medical College, Huazhong University of Science and Technology, Chibi, Hubei, PR China., Kouakanou L; Institute of Immunology, Christian-Albrechts-University Kiel, Kiel, Germany., Li J; Zhuhai Precision Medical Center, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Jinan University, Zhuhai, 519000, Guangdong, PR China.; The Biomedical Translational Research Institute, Jinan University, Guangzhou, 510632, Guangdong, PR China., He J; The Biomedical Translational Research Institute, Jinan University, Guangzhou, 510632, Guangdong, PR China., Yang J; Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, PR China., Hu Y; The Biomedical Translational Research Institute, Jinan University, Guangzhou, 510632, Guangdong, PR China., Chen Y; The Biomedical Translational Research Institute, Jinan University, Guangzhou, 510632, Guangdong, PR China., Lin L; The Biomedical Translational Research Institute, Jinan University, Guangzhou, 510632, Guangdong, PR China., Hao J; Zhuhai Precision Medical Center, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Jinan University, Zhuhai, 519000, Guangdong, PR China.; The Biomedical Translational Research Institute, Jinan University, Guangzhou, 510632, Guangdong, PR China., Li J; The Biomedical Translational Research Institute, Jinan University, Guangzhou, 510632, Guangdong, PR China., Chen J; Fuda Cancer Hospital, Faculty of Medical Science, Jinan University, Guangzhou, 510665, Guangdong, PR China., Li M; The Biomedical Translational Research Institute, Jinan University, Guangzhou, 510632, Guangdong, PR China., Wu Q; The Biomedical Translational Research Institute, Jinan University, Guangzhou, 510632, Guangdong, PR China., Peters C; Institute of Immunology, Christian-Albrechts-University Kiel, Kiel, Germany., Zhou Q; Zhuhai Precision Medical Center, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Jinan University, Zhuhai, 519000, Guangdong, PR China.; The Biomedical Translational Research Institute, Jinan University, Guangzhou, 510632, Guangdong, PR China., Li J; Zhuhai Precision Medical Center, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Jinan University, Zhuhai, 519000, Guangdong, PR China.; The Biomedical Translational Research Institute, Jinan University, Guangzhou, 510632, Guangdong, PR China., Liang Y; Fuda Cancer Hospital, Faculty of Medical Science, Jinan University, Guangzhou, 510665, Guangdong, PR China., Wang X; Fuda Cancer Hospital, Faculty of Medical Science, Jinan University, Guangzhou, 510665, Guangdong, PR China., Han B; Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, PR China., Ma M; Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, PR China., Kabelitz D; Institute of Immunology, Christian-Albrechts-University Kiel, Kiel, Germany. dietrich.kabelitz@uksh.de., Xu K; The Biomedical Translational Research Institute, Jinan University, Guangzhou, 510632, Guangdong, PR China.; Fuda Cancer Hospital, Faculty of Medical Science, Jinan University, Guangzhou, 510665, Guangdong, PR China., Tu W; Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, PR China., Wu Y; Zhuhai Precision Medical Center, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Jinan University, Zhuhai, 519000, Guangdong, PR China. tyzwu@jnu.edu.cn.; The Biomedical Translational Research Institute, Jinan University, Guangzhou, 510632, Guangdong, PR China. tyzwu@jnu.edu.cn., Yin Z; Zhuhai Precision Medical Center, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Jinan University, Zhuhai, 519000, Guangdong, PR China. zhinan.yin@yale.edu.; The Biomedical Translational Research Institute, Jinan University, Guangzhou, 510632, Guangdong, PR China. zhinan.yin@yale.edu.
Jazyk: angličtina
Zdroj: Cellular & molecular immunology [Cell Mol Immunol] 2021 Feb; Vol. 18 (2), pp. 427-439. Date of Electronic Publication: 2020 Sep 16.
DOI: 10.1038/s41423-020-0515-7
Abstrakt: 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 peripheral γδ T cells from healthy donors. Then, we used a humanized mouse model to validate the therapeutic efficacy of expanded γδ T cells in vivo; furthermore, the expanded γδ 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 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.
Databáze: MEDLINE
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