DC vaccine enhances CAR-T cell antitumor activity by overcoming T cell exhaustion and promoting T cell infiltration in solid tumors

Authors：Zhang, Miaomiao; Wang, Yuanyuan; Chen, Xinzu; Zhang, Fan; Chen, Jiannan; Zhu, Hongqiao; Li, Jun; Chen, Zhengliang; Wang, Aying; Xiao, Yao; Chen, Zilu; Dong, Yunfei; Yin, Xuechen; Ji, Feng; Liu, Jie; Liang, Junqing; Pan, Feiyan; Guo, Zhigang; He, Lingfeng^*

Source：Clinical & Translational Oncology, 2023, 25(10): 2972-2982.

DOI：10.1007/s12094-023-03161-1

• MSLN CAR-T
• DC vaccine
• Solid tumor
• Infiltration
• Persistence

Objective 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. Methods 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. Results 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. Conclusion 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.

• Institution
  南方医科大学; 1