Human leukocyte antigen-presented tumor antigens (pHLA tumor antigens) (pHLA)

Human leukocyte antigen (HLA)-presented tumor antigens are short peptide sequences derived from intracellular proteins that are displayed on the surface of cancer cells to be recognized by T cells. These antigens are categorized into tumor-specific antigens (TSAs), or neoantigens, which result from somatic mutations unique to the tumor, and tumor-associated antigens (TAAs), which are normal proteins that are overexpressed or inappropriately expressed in malignant cells (Schumacher & Schreiber, Science 2015). The presentation of these peptides by HLA Class I or II molecules is a fundamental requirement for the adaptive immune system to identify and eliminate cancerous cells (NCI, 2023). Therapeutic interventions such as personalized cancer vaccines and TCR-engineered T-cell therapies are designed to exploit these targets to induce a robust and specific anti-tumor immune response (Nature Reviews Drug Discovery, 2021). Because neoantigens are not present in healthy tissues, they represent highly specific targets that minimize the risk of systemic autoimmunity. However, the effectiveness of targeting these antigens can be limited by tumor heterogeneity and the ability of cancer cells to downregulate HLA expression as a mechanism of immune evasion (PubMed, 2022). Current clinical developments, including mRNA-based vaccines, continue to refine the selection and delivery of these patient-specific targets to improve outcomes in various solid tumors.

Other names

NeoantigensTumor-specific antigens (TSAs)Tumor-associated antigens (TAAs)HLA-restricted tumor peptidesCancer-testis antigens (CTAs)Mutation-derived antigensPatient-specific tumor antigens

Induction of antigen-specific T-cell responses or direct T-cell redirection to tumor cells via recognition of peptide-HLA complexes.