Neoantigen vaccine: an emerging tumor immunotherapy

Abstract

Genetic instability of tumor cells often leads to the occurrence of a large number of mutations, and expression of non-synonymous mutations can produce tumor-specific antigens called neoantigens. Neoantigens are highly immunogenic as they are not expressed in normal tissues. They can activate CD4+ and CD8+ T cells to generate immune response and have the potential to become new targets of tumor immunotherapy. The development of bioinformatics technology has accelerated the identification of neoantigens. The combination of different algorithms to identify and predict the affinity of neoantigens to major histocompatibility complexes (MHCs) or the immunogenicity of neoantigens is mainly based on the whole-exome sequencing technology. Tumor vaccines targeting neoantigens mainly include nucleic acid, dendritic cell (DC)-based, tumor cell, and synthetic long peptide (SLP) vaccines. The combination with immune checkpoint inhibition therapy or radiotherapy and chemotherapy might achieve better therapeutic effects. Currently, several clinical trials have demonstrated the safety and efficacy of these vaccines. Further development of sequencing technologies and bioinformatics algorithms, as well as an improvement in our understanding of the mechanisms underlying tumor development, will expand the application of neoantigen vaccines in the future.

Keywords: Immunotherapy; Malignancy; Neoantigen; Tumor; Vaccine.

Fig. 1

Mutations in tumor tissue produce neoantigens. Clonal neoantigens can be expressed by a large number of proliferating tumor cells. Various software packages were used to compare the sequence differences between tumor cells and normal cells, and to predict and prioritize the immunogenicity of antigens for screening the optimal tumor neoantigens

Fig. 2

Major types of neoantigen vaccine. In vivo, neoantigens are eventually presented to CD4+ T cells and CD8+ T cells to induce specific immune responses and achieve anti-tumor effects

Fig. 3

Combination of neoantigen vaccines with other therapies. Combination of neoantigen vaccines with the checkpoint inhibition therapy can relieve the tumor cell-mediated inhibition of effector T cells. Radiotherapy and chemotherapy can assist vaccines play a better effect. Drugs targeting the immunosuppressive factors in the tumor microenvironment were administered to circumvent the inactivation of T cells by various molecules and cells in the tumor microenvironment. In combination with CAR-T therapy, T cells specifically targeting neoantigens were cultured in vitro and then injected into the body to generate effector T cells and memory T cells, thereby enhancing the anti-tumor effect