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, Zhenyu Ding
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. The generation of neoantigen-specific T cells for adoptive cell therapy (ACT) is challenging. Here the authors conveniently produce ACT-amenable neoantigen-reactive T cells (NRT) by inducing neoantigen-specific immune responses in vivo via dendritic cell vaccination and find adoptive transfer of such NRTs in a pre-immunized mouse model of lung cancer improves ACT efficacy and induces tumor regression.