Shared tumor neoantigen

Shared tumor neoantigens are immunogenic peptides resulting from recurrent somatic mutations in oncogenic driver genes, such as KRAS, TP53, and PIK3CA, that are found across multiple cancer patients (Nature Reviews Cancer, 2021). Unlike patient-specific neoantigens, these "public" neoantigens enable the creation of "off-the-shelf" therapeutic products, including vaccines and TCR-engineered T-cell (TCR-T) therapies (Science, 2022). These antigens are presented by specific Human Leukocyte Antigen (HLA) molecules on the tumor cell surface, allowing for highly specific recognition by the adaptive immune system while sparing healthy tissues that lack these mutations (Frontiers in Immunology, 2020). Therapeutic interventions like ELI-002 and mRNA-5671 aim to stimulate or provide T-cells that specifically target these mutant epitopes (ClinicalTrials.gov, 2023). While promising, the efficacy of targeting shared neoantigens is often limited by the requirement for patients to possess both the specific mutation and the matching HLA allele (Journal of Hematology & Oncology, 2021). Furthermore, tumors may develop resistance through immune escape mechanisms such as the downregulation of HLA molecules or the loss of the target antigen (Nature Communications, 2023). Despite these challenges, shared neoantigens represent a significant advancement in precision oncology by combining the specificity of neoantigen targeting with the scalability of traditional pharmaceuticals.

Other names

Public neoantigensCommon neoantigensRecurrent neoantigensOff-the-shelf neoantigens

Induction of antigen-specific T-cell mediated cytotoxicity through the recognition of mutant peptide-MHC complexes.