Tumor neoantigens: Novel strategies for application of cancer immunotherapy

Abstract

Neoantigen-targeted immunotherapy is a rapidly advancing field that holds great promise for treating cancer. The recognition of antigens by immune cells is a crucial step in tumor-specific killing, and neoantigens generated by mutations in cancer cells possess high immunogenicity and are selectively expressed in tumor cells, making them an attractive therapeutic target. Currently, neoantigens find utility in various domains, primarily in the realm of neoantigen vaccines such as DC vaccines, nucleic acid vaccines, and synthetic long peptide vaccines. Additionally, they hold promise in adoptive cell therapy, encompassing tumor-infiltrating cells, T cell receptors, and chimeric antigen receptors which are expressed by genetically modified T cells. In this review, we summarized recent progress in the clinical use of tumor vaccines and adoptive cell therapy targeting neoantigens, discussed the potential of neoantigen burden as an immune checkpoint in clinical settings. With the aid of state-of-the-art sequencing and bioinformatics technologies, together with significant advancements in artificial intelligence, we anticipated that neoantigens will be fully exploited for personalized tumor immunotherapy, from screening to clinical application.

Keywords: Adoptive T cell therapy; Chimeric antigen receptor; Immunotherapy; Tumor vaccine.

Figure 1. Major types of neoantigen vaccine. In tumor microenvironment, neoantigen vaccines can activate CD8+ T cells and CD4+ T cells to kill tumor cells.

Figure 2. Direct infusion of in vitro expanded TILs.

Figure 3. Different strategies of adoptive cell therapy. There are two primary methods to engineer T cells in vitro. The first involves equipping T cells with neoantigen-specific TCR (neoTCR), called TCR-T. The second approach entails replacing the original TCR with a chimeric antigen receptor and called CAR-T.