Mutant peptide–Human Leukocyte Antigen complex (pHLA) (pHLA)

Mutant peptide–Human Leukocyte Antigen (HLA) complexes, often referred to as neoantigen-HLA complexes, are molecular structures formed when somatic mutations in a tumor's genome result in novel protein sequences that are processed and presented on the cell surface by HLA molecules (Schumacher & Schreiber, 2015, Science). These complexes are highly specific to cancer cells, as the underlying mutations are absent in healthy tissues, making them ideal targets for precision immunotherapy (Blass & Ott, 2021, Nature Reviews Clinical Oncology). The biological function of these complexes is to serve as red flags for the immune system, specifically for recognition by the T-cell receptor (TCR) of CD8+ or CD4+ T cells (Sahin & Türeci, 2018, Science). Therapeutic strategies targeting these complexes include personalized cancer vaccines, TCR-engineered T-cell (TCR-T) therapies, and TCR-like antibodies or bispecific molecules (Yarchoan et al., 2017, NEJM). Because these targets are tumor-specific, they offer the potential for high efficacy with reduced off-target toxicity compared to traditional therapies. However, challenges such as HLA downregulation by tumors and the high degree of patient-specific polymorphism in HLA alleles complicate the broad application of these treatments (Textor et al., 2016, Frontiers in Immunology).

Other names

Neoantigen-HLA complexMutant peptide-MHC complexTumor-specific antigen-HLA complexNeoepitope-HLA complexTSA-HLA complex

Recognition by T-cell receptors (TCRs) or TCR-mimetic antibodies to trigger cytotoxic T-lymphocyte-mediated destruction of tumor cells.