Patient-specific tumor neoantigens (Neoantigens)

Patient-specific tumor neoantigens are unique peptides derived from non-synonymous somatic mutations, such as single-nucleotide variants or frameshifts, that occur exclusively within a patient's tumor cells (Nature Reviews Cancer, 2021). These neoantigens are processed and presented on the cell surface by Major Histocompatibility Complex (MHC) Class I and Class II molecules, where they can be recognized by the host's CD8+ and CD4+ T cells, respectively (Science, 2017). Because these antigens are absent from the normal proteome, they are highly immunogenic and bypass central thymic tolerance, making them ideal targets for highly specific precision immunotherapy (Frontiers in Immunology, 2020). Therapeutic strategies targeting these neoantigens include personalized vaccines—such as mRNA, peptide, or viral vector platforms—and adoptive cell therapies using T cells engineered with neoantigen-specific receptors (Cell, 2020). By targeting these unique markers, clinicians aim to induce a robust, tumor-specific immune response while minimizing off-target toxicity to healthy organs (Journal of Hematology & Oncology, 2019). The identification and selection of these neoantigens rely heavily on next-generation sequencing and advanced bioinformatic algorithms to predict which mutations will result in stable peptide-MHC complexes (Nature, 2017).

Other names

Tumor-specific antigens (TSAs)NeoepitopesSomatic mutation-derived antigensPersonalized tumor antigensMutation-derived neoantigens

Induction of de novo neoantigen-specific T-cell responses or expansion of existing neoantigen-specific T-cell clones to selectively eliminate tumor cells expressing the unique mutation-derived peptides.