Patient-specific tumor neoantigen peptides bound to Major Histocompatibility Complex (MHC) class I and II (Neoantigen-MHC complex)

Patient-specific tumor neoantigen peptides bound to Major Histocompatibility Complex (MHC) class I and II represent a highly personalized class of therapeutic targets in oncology. These neoantigens arise from somatic mutations within a patient's tumor, resulting in novel protein sequences that the immune system recognizes as non-self (Schumacher & Schreiber, 2015, Science). When these peptides are processed and presented by dendritic cells on MHC molecules, they serve as the primary signal for the activation of cytotoxic CD8+ and helper CD4+ T cells (Sahin & Türeci, 2018, Nature). This interaction is the cornerstone of personalized cancer vaccines, such as mRNA-4157/V940 and Autogene cevumeran, which aim to direct the immune system to selectively eliminate malignant cells while sparing healthy tissue (Weber et al., 2024, The Lancet). Because neoantigens are unique to each patient's tumor, they minimize the risk of off-target autoimmunity compared to shared tumor-associated antigens. Current therapeutic strategies involve identifying these mutations through genomic sequencing and delivering them via mRNA, DNA, or peptide-based platforms to stimulate a robust, tumor-specific immune response (Hu et al., 2021, Nature Reviews Immunology).

Other names

Tumor-specific neoantigens (TSNAs)NeoepitopesPersonalized tumor antigensPeptide-MHC (pMHC) complexesTumor-specific antigens

Induction of tumor-specific T-cell responses through the presentation of somatic mutation-derived epitopes by dendritic cells to naive T cells, leading to the expansion of cytotoxic and helper T-cell populations that recognize and eliminate tumor cells.