Patient-specific tumor-associated antigens and neoantigen-derived peptide–MHC complexes (Neoantigen-pMHC)

Patient-specific tumor-associated antigens and neoantigen-derived peptide–MHC (pMHC) complexes are unique molecular signatures found on the surface of malignant cells, serving as critical targets for personalized immunotherapy (Nature Reviews Cancer, 2021). These complexes are formed when somatic mutations—such as point mutations, insertions, or deletions—create novel protein sequences (neoantigens) that are processed and presented by the patient's Major Histocompatibility Complex (MHC) molecules (Science, 2017). Unlike traditional tumor-associated antigens, neoantigens are not expressed in normal tissues, which significantly reduces the risk of autoimmune cross-reactivity and bypasses central thymic tolerance (Frontiers in Immunology, 2020). Therapeutic interventions, including personalized mRNA vaccines like mRNA-4157 and adoptive TCR-T cell therapies, aim to elicit or enhance a robust cytotoxic T-cell response specifically against these neoepitopes (The Lancet, 2023). While highly promising for precision oncology, the clinical application of these targets requires sophisticated genomic sequencing and bioinformatic prediction tools to identify the most immunogenic peptides for each individual patient (Journal of Hematology & Oncology, 2021). Challenges remain regarding the heterogeneity of neoantigen expression and the potential for tumor immune evasion via MHC downregulation or loss of the targeted mutation (Nature, 2019).

Other names

NeoantigensTumor-specific antigens (TSAs)NeoepitopespMHC complexesPersonalized tumor antigensTumor-associated neoantigens

Induction of a specific T-cell mediated immune response by presenting tumor-specific mutant peptides to the immune system, leading to the recognition and lysis of tumor cells.