Patient-specific tumor neoantigen presented on Major Histocompatibility Complex (pMHC)

Patient-specific tumor neoantigens presented on Major Histocompatibility Complex (MHC) are unique peptides derived from somatic mutations within a patient's tumor cells [8, 12]. These mutations, which include single nucleotide variants, frameshifts, and gene fusions, result in non-self proteins that are processed and displayed on the cell surface by MHC class I or II molecules [10, 12, 16]. Because these neoantigens are absent in healthy tissues, they are not subject to central immune tolerance, allowing them to trigger robust and highly specific T-cell responses [8, 12, 14]. Therapeutic approaches such as personalized vaccines (mRNA or peptide-based) and adoptive T-cell therapies (TCR-T) leverage these targets to direct the immune system to selectively eliminate cancer cells [1, 11, 18]. By targeting these individualized markers, clinicians can achieve high precision in oncology, potentially reducing the side effects associated with traditional therapies [1, 9]. However, the effectiveness of these treatments can be limited by tumor-mediated immune suppression or the loss of MHC expression [2, 13]. Additionally, the requirement for patient-specific manufacturing presents significant logistical and temporal challenges in clinical settings [1, 5, 16].

Other names

Tumor-specific neoantigen (TSNA)NeoepitopeMutation-derived antigenMHC-restricted neoantigenIndividualized neoantigen therapy (INT)Patient-specific neoantigen

Recognition of mutation-derived peptide-MHC complexes by T-cell receptors (TCRs), leading to the activation of cytotoxic T lymphocytes and subsequent lysis of tumor cells [8, 11, 13].