Personalized cancer antigens (Neoantigens) (Neoantigens)

Personalized cancer antigens, commonly known as neoantigens, are novel peptides derived from non-synonymous somatic mutations that occur specifically within a patient's tumor cells (National Cancer Institute, 2024). Because these antigens are not encoded by the normal human genome, they are not subject to central thymic tolerance, making them highly immunogenic and ideal targets for precision immunotherapy (Sahin & Türeci, Science, 2018). The identification of these antigens involves high-throughput sequencing of the tumor exome and transcriptome, followed by computational modeling to predict which mutated peptides will successfully bind to the patient's specific Human Leukocyte Antigen (HLA) molecules (Hu et al., Nature Reviews Genetics, 2021). Therapeutic interventions, such as personalized mRNA or peptide-based vaccines, are designed to prime the patient's immune system to recognize these unique molecular signatures, thereby directing cytotoxic T-lymphocytes to selectively destroy malignant cells while sparing healthy tissue (Blass & Ott, Nature Reviews Clinical Oncology, 2021). This approach is currently being evaluated in numerous clinical trials, often in combination with immune checkpoint inhibitors, to overcome tumor-induced immunosuppression and improve durable response rates in various solid tumors (Nature, 2023). Despite their promise, challenges remain regarding the time-intensive manufacturing process and the potential for tumors to evolve and lose the targeted antigens over time.

Other names

NeoantigensTumor-specific antigensTSAsMutation-derived antigensPersonalized neoantigensTumor-specific neoantigens

Induction of de novo T-cell responses against tumor-specific mutations and expansion of existing neoantigen-specific T-cell clones to eliminate malignant cells through recognition of mutated peptides presented on Major Histocompatibility Complex (MHC) molecules.