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

• Miaomiao Zhang ^[3] ; Yuanyuan Wang ^[3] ; Xinzu Chen ^[3] ; Fan Zhang ^[3] ; Jiannan Chen ^[3] ; Hongqiao Zhu ^[3] ; Jun Li ^[4] ; Zhengliang Chen ^[4] ; Aying Wang ^[1] ; Yao Xiao ^[2] ; Zilu Chen ^[2] ; Yunfei Dong ^[3] ; Xuechen Yin ^[3] ; Feng Ji ^[3] ; Jie Liu ^[3] ; Junqing Liang ^[5] ; Feiyan Pan ^[3] ; Zhigang Guo ^[3] ; Lingfeng He ^[3]
  1. [1] Southern Medical University

     Southern Medical University

     China

     
  2. [2] Nanjing University of Chinese Medicine

     Nanjing University of Chinese Medicine

     China

     
  3. [3] Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing, 210023, China
  4. [4] Nanjing Blue Shield Biotechnology Co., Ltd., Nanjing, 210023, China
  5. [5] Inner Mongolia Autonomous Region Cancer Hospital, Hohhot, 010010, China

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• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 25, Nº. 10 (October), 2023, págs. 2972-2982
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • 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.