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

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Abstract

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.

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Data availability

The authors state that all data is available from the text or corresponding authors.

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Acknowledgements

Thanks to all the partners who were helpful to the article, the guidance provided by the teacher, the platform provided by the school, and the funding from the state.

Funding

National Natural Science Foundation of China, 81872284, Miaomiao Zhang

Author information

Author notes

  1. Miaomiao Zhang and Yuanyuan Wang are contributed equally to this manuscript.

Authors and Affiliations

  1. Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing, 210023, China

    Miaomiao Zhang, Yuanyuan Wang, Xinzu Chen, Fan Zhang, Jiannan Chen, Hongqiao Zhu, Yunfei Dong, Xuechen Yin, Feng Ji, Jie Liu, Feiyan Pan, Zhigang Guo & Lingfeng He

  2. Nanjing Blue Shield Biotechnology Co., Ltd., Nanjing, 210023, China

    Jun Li & Zhengliang Chen

  3. Department of Respiratory and Critical Care Medicine, The First School of Clinical Medicine, Jinling Hospital, Southern Medical University, Nanjing, 210018, China

    Aying Wang

  4. Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China

    Yao Xiao & Zilu Chen

  5. Inner Mongolia Autonomous Region Cancer Hospital, Hohhot, 010010, China

    Junqing Liang

Authors
  1. Miaomiao Zhang
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Contributions

MZ, YW and LH proposed the research direction and designed the experimental scheme. MZ, YW, XC, FZ, JC, and HZ organized and analyzed the data. MZ, YW, XC, FZ, JC, HZ, JL2, and ZC2 interpreted the data; MZ, YW, and XC wrote and revised the manuscript; MZ, YW, XC, FZ, JC, HZ, JL2, ZC2, AW, YX, ZC4, YD, XY, FJ, JL1, JL5, FP, ZG, and LH provided funding and platforms for the experiments. LH supervised the study.

Corresponding author

Correspondence to Lingfeng He.

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The authors declare that they have no conflict of interest.

Ethical approval

All in vivo animal experiments were approved by the Committee on the Ethics of Animal Experiments of Nanjing Normal University (IRB#2020–0047).

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Zhang, M., Wang, Y., Chen, X. et al. DC vaccine enhances CAR-T cell antitumor activity by overcoming T cell exhaustion and promoting T cell infiltration in solid tumors. Clin Transl Oncol 25, 2972–2982 (2023). https://doi.org/10.1007/s12094-023-03161-1

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  • DOI: https://doi.org/10.1007/s12094-023-03161-1

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