Neoantigen: A New Breakthrough in Tumor Immunotherapy

Abstract

Cancer immunotherapy works by stimulating and strengthening the body's anti-tumor immune response to eliminate cancer cells. Over the past few decades, immunotherapy has shown remarkable efficacy in the treatment of cancer, particularly the success of immune checkpoint blockade targeting CTLA-4, PD-1 and PDL1, which has led to a breakthrough in tumor immunotherapy. Tumor neoantigens, a new approach to tumor immunotherapy, include antigens produced by tumor viruses integrated into the genome and antigens produced by mutant proteins, which are abundantly expressed only in tumor cells and have strong immunogenicity and tumor heterogeneity. A growing number of studies have highlighted the relationship between neoantigens and T cells' recognition of cancer cells. Vaccines developed against neoantigens are now being used in clinical trials in various solid tumors. In this review, we summarized the latest advances in the classification of immunotherapy and the process of classification, identification and synthesis of tumor-specific neoantigens, as well as their role in current cancer immunotherapy. Finally, the application prospects and existing problems of neoantigens were discussed.

Keywords: immunotherapy; neoantigen; personalized cancer immunotherapy; tumor-specific antigens; vaccine.

Figure 1

Classification of immunotherapies. Immunotherapy is usually divided into passive immunotherapy and active immunotherapy. Active immunotherapy is mainly cancer vaccines. Passive immunotherapy mainly includes adoptive cell therapy, oncolytic viruses, and monoclonal antibodies.

Figure 2

Classification of neoantigens. Neoantigens can be classified into two categories: shared neoantigens and personalized neoantigens. Shared neoantigens refer to mutated antigens that are common across different cancer patients and not present in the normal genome. Personalized neoantigens refer to mutated antigens that are unique to most neoantigens and completely different from patient to patient.

Figure 3

Identification of neoantigens. First, the new antigens were found by high-throughput sequencing, then screened by algorithm and mass spectrometry, and finally verified by experiment.

Figure 4

Synthesis of neoantigen. First, tumor and normal tissue samples were obtained. Then, by comparing the sequencing results of the two groups of samples, the mutated gene of the tumor was identified. Using computer, mass spectrometry or experimental methods to screen the gene sequences that are most likely to become tumor neoantigens, and finally these mutated genes can be designed into vaccines, which can take many forms, such as peptide vaccines, dendritic cell vaccines, RNA vaccines, etc.