Patient-specific neoantigen–HLA complex (NeoAg-HLA)

Patient-specific neoantigen–HLA complexes are molecular assemblies on the surface of cancer cells that present mutated protein fragments to the immune system (Schumacher & Schreiber, 2015, Science). These fragments, or neoantigens, result from tumor-specific somatic mutations—such as non-synonymous single nucleotide variants (SNVs), insertions, or deletions—and are not expressed by healthy cells (Sahin & Türeci, 2018, Science). When these mutated peptides are processed and loaded onto Human Leukocyte Antigen (HLA) molecules, they can be recognized as "non-self" by T-cell receptors (TCRs) (Blass & Ott, 2021, Nature Reviews Clinical Oncology). This recognition is a critical step in the natural anti-tumor immune response and serves as the foundation for personalized cancer immunotherapies (Ott et al., 2017, Nature). Therapeutic strategies targeting these complexes include personalized mRNA or peptide vaccines and adoptive cell transfers using TCR-engineered T cells (Hu et al., 2021, Nature Reviews Immunology). By focusing on patient-specific mutations, these treatments aim to achieve high specificity and potency while reducing the risk of autoimmune toxicity (Yarchoan et al., 2017, New England Journal of Medicine). However, the effectiveness of these therapies can be limited by tumor heterogeneity and the potential for immune escape through the downregulation of HLA molecules or the loss of the target antigen.

Other names

Tumor-specific neoantigen-HLA complexNeoepitope-MHC complexMutant peptide-HLA complexpHLA complexTumor-specific antigen-MHC complex

Recognition by endogenous or engineered T-cell receptors (TCRs) to induce cytotoxic T-lymphocyte-mediated lysis of tumor cells (Schumacher & Schreiber, 2015, Science).