Patient-specific neoantigen peptides presented on Human Leukocyte Antigen (HLA) molecules (Neoantigen-HLA complex)

Patient-specific neoantigen peptides presented on Human Leukocyte Antigen (HLA) molecules are unique protein fragments derived from somatic mutations within a patient's tumor cells (Science, 2015, 348(6230):69-74). These peptides are processed and displayed on the cell surface by HLA class I or II molecules, where they act as highly specific targets for the adaptive immune system (Nature, 2017, 547(7662):222-226). Because these neoantigens are not present in the normal genome, they are recognized as foreign by T-cells, bypassing central tolerance and reducing the risk of autoimmune reactions. Therapeutic interventions, such as personalized mRNA vaccines (e.g., mRNA-4157) or peptide-based vaccines, are designed to prime and expand the patient's own T-cell repertoire against these specific complexes (Nature, 2017, 547(7662):217-221). The clinical utility of these targets relies on advanced genomic sequencing and bioinformatic pipelines to identify and prioritize the most immunogenic mutations for each individual patient.

Other names

Tumor-specific neoantigensNeoepitopesPersonalized neoantigensMHC-restricted neoantigensTSNAspHLA complexes

Induction of a de novo T-cell response or expansion of existing neoantigen-specific T-cells that recognize the peptide-HLA complex on tumor cells, leading to perforin/granzyme-mediated apoptosis (Nature Reviews Cancer, 2021, 21(5):283-300).