Patient-specific tumor-associated antigen presented on Major Histocompatibility Complex (pMHC) (Neoantigen)

Patient-specific tumor-associated antigens, commonly known as neoantigens, are unique peptides derived from somatic mutations (such as SNVs, indels, or gene fusions) that occur exclusively within a patient's tumor cells (Schumacher & Schreiber, 2015, Science). These mutated proteins are processed by the proteasome and presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, forming a peptide-MHC (pMHC) complex (Blass & Ott, 2021, Nature Reviews Clinical Oncology). This complex serves as a critical target for the adaptive immune system, specifically for CD8+ and CD4+ T-cells, which recognize the mutated peptide as non-self (NCI Dictionary of Cancer Terms). Because neoantigens are absent from normal tissues, they are highly specific targets for immunotherapy, reducing the risk of off-target toxicity and bypassing central immune tolerance (Sahin & Türeci, 2018, Science). Therapeutic strategies targeting these pMHC complexes include personalized mRNA or peptide vaccines, such as mRNA-4157 and BNT122, as well as adoptive cell therapies like tumor-infiltrating lymphocytes (TILs). These treatments aim to expand the repertoire of neoantigen-specific T-cells to induce a durable anti-tumor response, though effectiveness can be limited by tumor heterogeneity or the loss of HLA expression.

Other names

NeoantigenTumor-specific antigenTSAMutation-derived antigenpMHC complexPersonalized tumor antigenTumor-specific neoantigen

Induction of antigen-specific T-cell responses through the presentation of mutated peptides on MHC molecules, leading to the recognition and lysis of tumor cells by cytotoxic T-lymphocytes.