Major Histocompatibility Complex class I and class II molecules presenting patient-specific neoepitope peptides (MHC-neoepitope complex)

The Major Histocompatibility Complex (MHC) class I and II molecules presenting patient-specific neoepitope peptides represent a cornerstone of personalized cancer immunotherapy. Neoepitopes are novel peptides derived from somatic mutations unique to an individual's tumor, which are processed and displayed on the cell surface by HLA molecules (the human version of MHC). Because these neoantigens are not present in healthy tissues, they are recognized as foreign by the immune system, minimizing central tolerance and providing a highly specific target for T-cell recognition. (Source: Nature Reviews Cancer, 2021; PubMed: 34155363). Therapeutic strategies targeting these complexes include personalized neoantigen vaccines (mRNA or peptide-based) and adoptive cell therapies using T-cell receptors (TCRs) engineered to recognize specific neoepitope-MHC combinations. These interventions aim to stimulate or provide a robust T-cell response that selectively destroys malignant cells while sparing normal tissue. However, the efficacy of these treatments can be limited by the heterogeneity of tumor mutations and the mechanisms tumors use to escape immune detection, such as the loss of MHC expression. (Source: Frontiers in Immunology, 2020; PubMed: 32117319).

Other names

HLA-neoantigen complexNeoepitope-MHC complexTumor-specific neoantigen (TSNA) presented by MHCPatient-specific neoantigen-HLA complexpMHC (peptide-MHC) complex

Binding of therapeutic T-cell receptors (TCRs) or vaccine-induced endogenous TCRs to the specific neoepitope-MHC complex to trigger targeted T-cell mediated cytotoxicity against tumor cells.