A dendritic cell vaccine for both vaccination and neoantigen-reactive T cell preparation for cancer immunotherapy in mice

Qing Li, Hao Zeng, Ting Liu, Peipei Wang, Rui Zhang, Binyan Zhao, Tang Feng, Yuling Yang, Jiumei Wu, Yue Zheng, Bailing Zhou, Yang Shu, Heng Xu, Li Yang () and Zhenyu Ding ()
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Qing Li: Sichuan University
Hao Zeng: Sichuan University
Ting Liu: Sichuan University
Peipei Wang: Sichuan University
Rui Zhang: Sichuan University
Binyan Zhao: Sichuan University
Tang Feng: Sichuan University
Yuling Yang: Sichuan University
Jiumei Wu: Sichuan University
Yue Zheng: Sichuan University
Bailing Zhou: Sichuan University
Yang Shu: Sichuan University
Heng Xu: Sichuan University
Li Yang: Sichuan University
Zhenyu Ding: Sichuan University

Nature Communications, 2024, vol. 15, issue 1, 1-24

Abstract: Abstract Adoptive cell transfer (ACT) using neoantigen-specific T cells is an effective immunotherapeutic strategy. However, the difficult isolation of neoantigen-specific T cells limits the clinical application of ACT. Here, we propose a method to prepare neoantigen-reactive T cells (NRT) for ACT following immunization with a tumor lysate-loaded dendritic cell (DC) vaccine. We show that the DC vaccine not only induces a neoantigen-reactive immune response in lung cancer-bearing mice in vivo, but also facilitate NRT cell preparation in vitro. Adoptive transfer of the NRTs as combinatorial therapy into DC vaccine-immunized, LL/2 tumor-bearing mice allows infiltration of the infused NRTs, as well as the enrichment of neoantigen reactive, non-ACT/NRT T cells into the tumor microenvironment with the function of these neoantigen-reactive T-cell receptors validated in vitro. In summary, we propose a method for preparing NRTs that increases ACT efficacy and paves the way to the design of personalized immunotherapies.

Date: 2024
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DOI: 10.1038/s41467-024-54650-y

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