Bispecific T-cells Expressing Polyclonal Repertoire of Endogenous γδ T-cell Receptors and Introduced CD19-specific Chimeric Antigen Receptor
Bispecific T-cells Expressing Polyclonal Repertoire of Endogenous γδ T-cell Receptors and Introduced CD19-specific Chimeric Antigen Receptor
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DOI：
10.1038/mt.2012.267
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发表时间：
2013-03-01
影响因子：
12.4
通讯作者：
Cooper, Laurence J. N.
中科院分区：
文献类型：
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作者：
Deniger, Drew C.;Switzer, Kirsten;Cooper, Laurence J. N.
尽管其他γδT细胞亚群表现出抗肿瘤活性，但γδT细胞的过继转移目前仅限于一个亚群（表达Vγ9V82 T细胞受体（TCR）），因为依赖氨基二磷酸盐作为唯一具有临床吸引力的γδT细胞增殖试剂。因此，我们开发了一种繁殖多克隆 γ δ T 细胞的方法，并通过表达 CD1 9 特异性嵌合抗原受体 (CAR) 使其具有双特异性。使用睡美人 (SB) 转座子和转座酶对外周血单核细胞 (PBMC) 进行电穿孔，以增强多个 γ δ T 细胞亚群中 CAR 的表达。 CAR(+)gamma delta T细胞在CD19(+)人工抗原呈递细胞(aAPC)上扩增，产生>10(9)个CAR(+)gamma delta T细胞
Even though other gamma delta T-cell subsets exhibit antitumor activity, adoptive transfer of gamma delta Tcells is currently limited to one subset (expressing V gamma 9V82 T-cell receptor (TCR)) due to dependence on aminobisphosphonates as the only clinically appealing reagent for propagating gamma delta T cells. Therefore, we developed an approach to propagate polyclonal gamma delta T cells and rendered them bispecific through expression of a CD1 9-specific chimeric antigen receptor (CAR). Peripheral blood mononuclear cells (PBMC) were electroporated with Sleeping Beauty (SB) transposon and transposase to enforce expression of CAR in multiple gamma delta T-cell subsets. CAR(+)gamma delta T cells were expanded on CD19(+) artificial antigen-presenting cells (aAPC), which resulted in >10(9) CAR(+)gamma delta T cells from