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

Neoantigen-derived peptide–Human Leukocyte Antigen (HLA) complexes are cell-surface markers formed when somatic mutations in a tumor's genome result in novel protein sequences that are processed and presented by the MHC machinery (Schumacher & Schreiber, Science 2015). These complexes are highly tumor-specific because the underlying mutations are absent in healthy germline DNA, providing an ideal target for precision immunotherapy with minimal risk of central tolerance (Blass & Ott, Nature Reviews Clinical Oncology 2021). Recognition of these neoepitopes by the T-cell receptor (TCR) of CD8+ or CD4+ T-cells is a critical step in the natural anti-tumor immune response and is the basis for several therapeutic modalities, including personalized mRNA vaccines and adoptive T-cell therapies (Sahin & Türeci, Science 2018). Because neoantigens are often unique to individual patients, they represent a cornerstone of personalized oncology, though their targeting is complicated by the heterogeneity of tumor mutations and the potential for immune evasion through the loss of HLA expression (Yadav et al., Nature 2014). Current clinical efforts focus on identifying these complexes through high-throughput sequencing and mass spectrometry to design vaccines and engineered T-cells that can selectively eliminate malignant cells while sparing normal tissue (Hu et al., Nature Reviews Immunology 2021).

Other names

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

Recognition by endogenous or engineered T-cell receptors (TCRs) leading to the activation of cytotoxic T-lymphocytes and subsequent apoptosis of the antigen-presenting tumor cell (Sahin & Türeci, Science 2018).