肿瘤细胞治疗研究
英文原题：Interleukin-15 and chemokine ligand 19 enhance cytotoxic effects of chimeric antigen receptor T cells using zebrafish xenograft model of gastric cancer.
这些发现表明15 19 CAR T细胞在杀伤胃癌细胞方面具有高效性，能有效避免脱靶效应，并可迁移至局部及转移部位以实现对肿瘤的长期监视。
嵌合抗原受体（CAR）T细胞已被证明对B细胞介导的恶性肿瘤治疗有效。目前，开发高效的工具以提供CAR T细胞用于治疗其他恶性肿瘤将具有重大影响。在本研究中，将白细胞介素（IL）-15和C-C基序趋化因子配体19（CCL19）引入基于自然杀伤组2D（NKG2D）的CAR中，生成15 19 CAR T细胞，其显著增加了T细胞扩增并促进了中央记忆T（T cm）细胞的产生。15 19 CAR T细胞对胃细胞系显示出比常规CAR T细胞更强的细胞毒性，并产生更高水平的IL-15和CCL-19，从而导致反应性T细胞趋化性增加和T细胞耗竭标志物表达减少。使用活体斑马鱼模型进行局部细胞毒性和转移性癌症的单细胞可视化。给予15 19 CAR T细胞导致胃癌异种移植肿瘤显著缩小，并在斑马鱼模型中扩增15 19 CAR T细胞。综上所述，这些发现表明15 19 CAR T细胞在杀伤胃癌细胞方面高效，能有效避免脱靶效应，并迁移至局部和转移部位以长期监测癌症。
Chimeric antigen receptor (CAR) T cells have been proven effective for the treatment of B-cell-mediated malignancies. Currently, the development of efficient tools that supply CAR T cells for the treatment of other malignancies would have great impact. In this study, interleukin (IL)-15 and C-C motif chemokine ligand 19 (CCL19) were introduced into natural killer group 2D (NKG2D)-based CARs to generate 15 19 CAR T cells, which remarkably increased T-cell expansion and promoted the production of central memory T (T cm ) cells. 15 19 CAR T cells showed greater cytotoxicity to gastric cell lines than conventional CAR T cells and produced higher levels of IL-15 and CCL-19, which resulted in increased responder T cell chemotaxis and reduced expression of T cell exhaustion markers. A live zebrafish model was used for single-cell visualization of local cytotoxicity and metastatic cancers. Administration of 15 19 CAR T cells resulted in significant shrinking of gastric cancer xenograft tumors and expansion of 15 19 CAR T cells in zebrafish models. Taken together, these findings demonstrate that 15 19 CAR T cells are highly efficient in killing gastric cancer cells, are effective to avoid off-target effects, and migrate to local and metastatic sites for long-term surveillance of cancers.
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