Patient-specific tumor neoantigen peptides presented by Major Histocompatibility Complex (MHC) molecules (NeoAg-MHC)

Patient-specific tumor neoantigen peptides presented by Major Histocompatibility Complex (MHC) molecules are unique protein fragments derived from somatic mutations within a patient's tumor (Nature Reviews Cancer, 2017). These mutations, which include single-nucleotide variants, insertions, and deletions, create novel epitopes that the immune system perceives as foreign because they are absent from the normal human proteome (Science, 2015). The presentation of these peptides by MHC Class I or Class II molecules is essential for the activation of CD8+ and CD4+ T cells, respectively, facilitating a highly targeted anti-tumor immune response (NEJM, 2019). Because neoantigens are strictly tumor-specific, they offer a high degree of therapeutic selectivity, significantly reducing the risk of autoimmune cross-reactivity compared to shared tumor-associated antigens. Current therapeutic strategies targeting these complexes include personalized mRNA vaccines, such as mRNA-4157, and autologous TCR-T cell therapies designed to recognize these specific peptide-MHC complexes (Nature, 2023). However, the clinical effectiveness of these treatments can be challenged by the high degree of tumor heterogeneity and the potential for tumors to evade detection through the loss of HLA expression (Cell, 2018).

Other names

NeoepitopesTumor-specific antigensTSAsPersonalized neoantigensMHC-restricted neoantigensPeptide-MHC complexespMHC

Therapeutic vaccines or adoptive cell therapies deliver or target specific mutated peptide sequences that are processed and presented by the patient's MHC molecules, leading to the activation and expansion of cytotoxic T-lymphocytes (CTLs) that specifically recognize and eliminate neoantigen-expressing tumor cells (Nature Reviews Drug Discovery, 2021).