Neoantigen peptide–Human Leukocyte Antigen complex (Neoantigen-HLA complex)

Neoantigen peptide–Human Leukocyte Antigen (HLA) complexes are unique molecular signatures found on the surface of tumor cells, resulting from somatic mutations that create novel, non-self protein sequences. These mutant peptides are processed intracellularly and presented by HLA molecules, making them ideal targets for highly specific cancer immunotherapies because they are entirely absent in healthy tissues (Nature Reviews Cancer, 2021). Therapeutic strategies targeting these complexes include personalized cancer vaccines, T-cell receptor (TCR) engineered T-cells, and TCR-like antibodies or bispecific T-cell engagers (BiTEs) (Frontiers in Immunology, 2020). By engaging these complexes, the immune system can selectively identify and eliminate malignant cells while sparing normal cells, potentially reducing off-target toxicities compared to traditional therapies targeting tumor-associated antigens. However, the high degree of patient-specific heterogeneity and the potential for tumor immune escape through HLA downregulation necessitate highly personalized approaches to target identification and drug design (Journal of Hematology & Oncology, 2024).

Other names

Neoepitope-HLA complexTumor-specific antigen-MHC complexMutant peptide-MHC complexpHLA complexNeoantigen-MHC class I complexNeoantigen-MHC class II complex

Induction of de novo T-cell responses or redirection of engineered T-cells (TCR-T) and bispecific molecules to recognize and lyse tumor cells presenting mutant peptides via the T-cell receptor.