Tumor-specific neoantigen presented on Major Histocompatibility Complex (TSNA-MHC)

Tumor-specific neoantigens (TSNAs) are novel peptides arising from non-synonymous somatic mutations, insertions/deletions, or chromosomal translocations unique to cancer cells. These peptides are processed by the proteasome and presented on the cell surface by Major Histocompatibility Complex (MHC) Class I or II molecules (PMID: 28639998). Because TSNAs are absent from the normal proteome, they are recognized as foreign by the immune system, bypassing central thymic tolerance and significantly reducing the risk of off-target autoimmunity compared to tumor-associated antigens (PMID: 31019211). Therapeutic interventions, such as personalized mRNA or peptide vaccines and TCR-engineered T-cell therapies, aim to exploit these targets to elicit a robust, tumor-specific cytotoxic T-lymphocyte response (PMID: 30244163). The clinical relevance of TSNAs is underscored by their role as primary targets for endogenous T-cells during immune checkpoint blockade therapy, where high neoantigen load often correlates with better patient outcomes (PMID: 25517006). However, challenges remain regarding the high degree of intratumoral heterogeneity and the potential for tumors to lose MHC expression as a mechanism of acquired resistance.

Other names

NeoantigenNeoepitopeTumor-specific antigenTSAMutation-derived antigenPeptide-MHC complex

Induction of de novo T-cell responses or expansion of existing neoantigen-specific T-cells through vaccination or adoptive transfer of T-cell receptors (TCRs) specifically recognizing the peptide-MHC complex.