Background. Chimeric antigen receptor-modified T cell (CAR-T) therapy has great potential for treating malignant tumors, especially hematological malignancies. However, the therapeutic effect of solid tumors is limited. One of the most important factors is the homing of CAR-T cells to tumor tissues in vivo. Method. a recombinant adeno-associated virus 2 (AAV2) subtype carrying the CCL19 gene was used to pretreat the tumor before the Glypican-3 (GPC3) CAR-T treatment. The tumor tissue continuously expressed CCL19 and analyzed the tumor-suppressive effect of AAV-CCL19 on GPC3 CAR-T by in vitro and in vivo experiments. Result. Under the chemotaxis of CCL19, CAR-T cells had a significant increase in the degree of tumor tissue infiltration; also, the antitumor effect in vitro was significantly enhanced. AAV-CCL19 combined with GPC3 CAR-T significantly increased the survival time of mice. The aforementioned results showed that the combination of AAV-CCL19 and GPC3 CAR-T cells effectively increased the ability of CAR-T cells to go home into the tumor tissue, making the CAR-T cell treatment more effective. Conclusion. This study is expected to solve the dilemma in treating CAR-T cell solid tumors and achieve better clinical results.

中文翻译：

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AAV-CCL19和GPC3 CAR-T细胞联合治疗肝细胞癌

背景。嵌合抗原受体修饰的T细胞（CAR-T）疗法在治疗恶性肿瘤，尤其是血液系统恶性肿瘤方面具有巨大潜力。然而，实体瘤的治疗效果有限。最重要的因素之一是 CAR-T 细胞在体内归巢到肿瘤组织。方法。在 Glypican-3 (GPC3) CAR-T 治疗之前，使用携带CCL19基因的重组腺相关病毒 2 (AAV2) 亚型对肿瘤进行预处理。肿瘤组织持续表达CCL19，并通过体外和体内实验分析了AAV-CCL19对GPC3 CAR-T的抑癌作用。结果. 在CCL19的趋化作用下，CAR-T细胞的肿瘤组织浸润程度明显增加；此外，体外抗肿瘤作用显着增强。AAV-CCL19联合GPC3 CAR-T显着增加了小鼠的存活时间。上述结果表明，AAV-CCL19与GPC3 CAR-T细胞联合有效提高了CAR-T细胞回家进入肿瘤组织的能力，使CAR-T细胞治疗更加有效。结论。该研究有望解决CAR-T细胞实体瘤治疗的困境，取得更好的临床效果。