Individualized tumor neoantigens (ITN)

Individualized tumor neoantigens are unique peptides derived from somatic mutations within a patient's tumor that are not expressed by normal cells (Nature, 2017). These antigens arise from various genetic alterations, including non-synonymous single-nucleotide variants, frameshift mutations, and chromosomal translocations (Science, 2017). Because they are absent from the healthy proteome, they are recognized as non-self by the immune system, bypassing central thymic tolerance and reducing the risk of autoimmunity (NCI, 2023). Therapeutic strategies targeting these neoantigens involve the creation of personalized vaccines—using mRNA, DNA, or peptide platforms—or the engineering of T-cell receptors (TCRs) to specifically bind these neoepitopes (Cell, 2020). These interventions aim to prime and expand neoantigen-specific CD8+ cytotoxic T cells and CD4+ helper T cells to achieve targeted tumor lysis (NEJM, 2019). By targeting multiple neoantigens simultaneously, these treatments seek to overcome tumor heterogeneity and prevent immune escape. Current clinical development, such as the mRNA-4157/V940 program, often combines these personalized approaches with checkpoint inhibitors to maximize the anti-tumor immune response (ASCO, 2023). This target class represents a cornerstone of precision oncology, shifting the paradigm from one-size-fits-all treatments to patient-specific immunotherapy.

Other names

Tumor-specific antigensPersonalized neoantigensNeoepitopesSomatic mutation-derived antigensTSA

Induction of de novo T-cell responses or expansion of pre-existing neoantigen-specific T cells to recognize and eliminate tumor cells expressing unique somatic mutations.