Tumor-specific neoantigen-HLA complex (pHLA)

Tumor-specific neoantigen-HLA complexes are molecular structures on the surface of cancer cells consisting of a mutant peptide (neoantigen) bound to a Human Leukocyte Antigen (HLA) molecule. These neoantigens result from somatic mutations, such as single-nucleotide variants, frameshifts, or aberrant splicing, that are unique to the tumor and absent in healthy tissues. Because they are not present in the normal proteome, they bypass central thymic tolerance, allowing the immune system to recognize them as non-self with high specificity. Recognition of these complexes by T-cell receptors (TCRs) triggers the activation of cytotoxic T lymphocytes and helper T cells, leading to the targeted destruction of the tumor. Therapeutic approaches targeting these complexes include personalized mRNA or peptide vaccines, adoptive cell therapies using neoantigen-specific TCRs, and bispecific T-cell engagers. However, significant challenges remain, including the low density of these complexes on the cell surface and the potential for tumor resistance through the downregulation or loss of HLA expression.

Other names

Neoepitope-HLA complexNeoantigen-MHC complexMutant peptide-HLA complexTumor-specific antigen (TSA)-HLA complexPeptide-MHC complex (pMHC)

Recognition by T-cell receptors (TCRs) to trigger cytotoxic T-lymphocyte (CTL) mediated killing of tumor cells and induction of long-term immunological memory.