Asan Institute for Life Sciences and Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Division of Pediatric Hematology/Oncology, Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Anticancer Res. 2021 Dec;41(12):6031-6038. doi: 10.21873/anticanres.15422.
BACKGROUND/AIM: This study aimed to investigate the characteristics of human peripheral blood γδ T cells, which were expanded ex vivo in the presence of zoledronate (ZOL).
Human peripheral blood cells were cultured with IL-2 and IL-15 in the presence or absence of ZOL, which was added as a phospho-antigen, and their phenotypes were assessed by flow cytometry. Expanded γδ T cells were transduced with CD19 CAR vector, and the cytotoxicity was evaluated in vitro and in vivo by flow cytometry.
Ex vivo expansion did not hamper the expression of activating receptors. Interestingly, ZOL promoted the expression of CD226 (DNAM-1), TRAIL, and FAS-L in the Vδ1 subset of γδ T cells. Expanded γδ T cells containing CD19 CAR γδ T cells removed B cell lymphoma cells effectively in vivo.
γδ T cells could be a promising immunotherapeutic for cancer.
背景/目的:本研究旨在研究人外周血 γδ T 细胞的特征,这些细胞在唑来膦酸(ZOL)存在的情况下体外扩增。
用人外周血细胞在 IL-2 和 IL-15 的存在下培养,ZOL 作为磷酸抗原添加,并用流式细胞术评估其表型。扩增的 γδ T 细胞用 CD19 CAR 载体转导,并通过流式细胞术在体外和体内评估细胞毒性。
体外扩增并不妨碍激活受体的表达。有趣的是,ZOL 促进了 Vδ1 亚群 γδ T 细胞中 CD226(DNAM-1)、TRAIL 和 FAS-L 的表达。含有 CD19 CAR γδ T 细胞的扩增 γδ T 细胞可有效清除体内 B 细胞淋巴瘤细胞。
γδ T 细胞可能是一种有前途的癌症免疫疗法。