Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing, 210023, China.
Nanjing Blue Shield Biotechnology Co., Ltd., Nanjing, 210023, China.
Clin Transl Oncol. 2023 Oct;25(10):2972-2982. doi: 10.1007/s12094-023-03161-1. Epub 2023 Apr 20.
Great success has been achieved in CAR-T cell immunotherapy in the treatment of hematological tumors. However, it is particularly difficult in solid tumors, because CAR-T is difficult to enter interior and exert long-term stable immune effects. Dendritic cells (DCs) can not only present tumor antigens but also promote the infiltration of T cells. Therefore, CAR-T cells with the help of DC vaccines are a reliable approach to treat solid tumors.
To test whether DC vaccine could promote CAR-T cell therapy in solid tumors, DC vaccine was co-cultured with MSLN CAR-T cells. The in vitro effects of DC vaccine on CAR-T were assessed by measuring cell proliferation, cell differentiation, and cytokine secretion. Effects of DC vaccine on CAR-T were evaluated using mice with subcutaneous tumors in vivo. The infiltration of CAR-T was analyzed using immunofluorescence. The persistence of CAR-T in mouse blood was analyzed using real-time quantitative PCR.
The results showed that DC vaccine significantly enhanced the proliferation potential of MSLN CAR-T cells in vitro. DC vaccines not only promoted the infiltration of CAR-T cells, but also significantly improved the persistence of CAR-T in solid tumors in vivo.
In conclusion, this study has demonstrated that DC vaccine can promote CAR-T therapy in solid tumors, which provides the possibility of widespread clinical application of CAR-T cells in the future.
嵌合抗原受体 T 细胞（CAR-T）免疫疗法在治疗血液系统肿瘤方面取得了巨大成功。然而，在实体肿瘤中，CAR-T 治疗效果较差，因为 CAR-T 难以进入肿瘤内部并发挥长期稳定的免疫作用。树突状细胞（DC）不仅可以呈递肿瘤抗原，还可以促进 T 细胞浸润。因此，在 DC 疫苗的辅助下，CAR-T 细胞是治疗实体瘤的可靠方法。
为了验证 DC 疫苗是否可以促进 CAR-T 细胞治疗实体瘤，将 DC 疫苗与 MSLN CAR-T 细胞共培养。通过测量细胞增殖、细胞分化和细胞因子分泌，评估 DC 疫苗对 CAR-T 的体外作用。通过皮下肿瘤荷瘤小鼠模型评估 DC 疫苗对 CAR-T 的体内作用。通过免疫荧光分析 CAR-T 的浸润情况。通过实时定量 PCR 分析 CAR-T 在小鼠血液中的持续存在情况。
结果表明，DC 疫苗可显著增强 MSLN CAR-T 细胞的体外增殖潜力。DC 疫苗不仅促进了 CAR-T 细胞的浸润，而且还显著提高了 CAR-T 在体内实体肿瘤中的持久性。
总之，本研究表明 DC 疫苗可促进 CAR-T 治疗实体瘤，为 CAR-T 细胞在未来的广泛临床应用提供了可能。
