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.

Novel Tumor-Specific Antigens for Immunotherapy Identified From Multi-omics Profiling in Thymic Carcinomas

“…Furthermore, driver genes are required in order for tumor cells to tolerate chromosomal losses caused by CIN, while passenger gene-derived neoantigens may be lost without fitness impact to the cancer subclone (9,44). However, not all neoantigens provide promising efficacy for patients (46). Like the tumor neoantigen selection alliance (TESLA) which established standards and functional validation methods to develop efficacious and safe personalized tumor vaccines, our identified neoantigens also required experimental Although pembrolizumab showed encouraging clinical benefits in advanced TETs, with a response rate of 19% and 23% (6,7), it needs to be identified who would benefit from ICIs without having to take the unnecessary risk of immune-related adverse effects.…”

Liquid Biopsy, ctDNA Diagnosis through NGS

“…Tumor-specific mutations in the coding region of genes can produce mutant proteins which are not present in normal cells. These mutant proteins, called neoantigens, can activate the immune system to attack the cancer cells [75]. Neoantigens can either be commonly shared within patients or unique to specific patients.…”

Function and Molecular Mechanism of the DNA Damage Response in Immunity and Cancer Immunotherapy

“…Additionally, higher vertebrates employ a sophisticated adaptive immune system that includes antibodies as well as B and T lymphocytes with virtually limitless repertoires of receptors that mediate neutralization of foreign pathogens and removal malignant cells ( 24 – 26 ). To stimulate strong anti-tumor immune responses, cancer immunotherapy typically employs immune checkpoint inhibitors for the PD-1/PD-L1 and CTLA-4 pathways to amplify immune system responses and also to harnesses responses to neoantigens that are primarily tumor-specific antigens resulting from the higher mutation load in tumor cells ( 27 – 29 ). The validity of the PD-1/PD-L1 approach requires the functional MHC class I complex, which itself is often deleted during tumor evolution to escape immune regulation ( 30 ).…”