Antitumor effect of neoantigen-reactive T cells combined with PD1 inhibitor therapy in mouse lung cancer

Abstract

Purpose Neoantigens produced from mutations in tumors are important targets of T-cell-based immunotherapy and immune checkpoint blockade has been approved for treating multiple solid tumors. We investigated the potential benefit of adoptive neoantigen-reactive T (NRT) cells in combination with programmed cell death protein 1 inhibitor (anti-PD1) for treating lung cancer in a mouse model. Methods NRT cells were prepared by co-culturing T cells and neoantigen-RNA vaccine-induced dendritic cells. Then, adoptive NRT cells in combination with anti-PD1 were administered to tumor-bearing mice. Pre- and post-therapy cytokine secretion, antitumor efficacy, and tumor microenvironment (TME) changes were determined both in vitro and in vivo. Results We successfully generated NRT cells based on the 5 neoantigen epitopes identified in this study. NRT cells exhibited an enhanced cytotoxic phenotype in vitro and the combination therapy led to attenuated tumor growth. In addition, this combination strategy downregulated the expression of the inhibitory marker PD‐1 on tumor-infiltrating T cells and promoted the trafficking of tumor-specific T cells to the tumor sites. Conclusion The adoptive transfer of NRT cells in association with anti-PD1 therapy can exert an antitumor effect on lung cancer, and is a feasible, effective, and novel immunotherapy regimen for treating solid tumors. Supplementary Information The online version contains supplementary material available at 10.1007/s00432-023-04683-5.

Tumor-specific T cells in head and neck cancer have rescuable functionality and can be identified through single-cell co-culture

“…While PD-1/PD-L1-based therapies are well-founded, the efficacy of these agents may be constrained by other immune checkpoint pathways [11] . Further, these agents are limited by the functional capacity, absolute number, and tumor-specificity of effector T cells which they release from checkpoint inhibition [ 12 , 13 ].…”

Transplantable Murine Tumors in the Studies of Peptide Antitumor Vaccines

“…H. Qin et al performed a search for immunogenic neoantigens in the LLC cells. The immunization was carried out using adoptive transfer of the RNA vaccine-treated DC-induced T cells [ 52 ].…”