Neoantigen-Major Histocompatibility Complex (MHC) (NeoAg-MHC)

The Neoantigen-Major Histocompatibility Complex (MHC) is a molecular assembly consisting of a tumor-specific mutated peptide (neoantigen) bound to a Major Histocompatibility Complex molecule (Blass & Ott, Nature Reviews Clinical Oncology, 2021). These complexes are presented on the surface of antigen-presenting cells (APCs) to prime naive T cells or on tumor cells to serve as targets for cytotoxic T-cell destruction (Schumacher & Schreiber, Science, 2015). Because neoantigens result from somatic mutations unique to an individual's tumor, they are not found in healthy tissues, making the Neoantigen-MHC complex a highly specific target for personalized cancer immunotherapy (Sahin & Türeci, Science, 2018). Therapeutic interventions include personalized vaccines—delivered via mRNA, DNA, or peptides—and adoptive cell therapies using T-cell receptors (TCRs) engineered to recognize these specific complexes (Hu et al., Nature Reviews Immunology, 2021). The clinical success of targeting these complexes depends on the accurate identification of immunogenic neoepitopes and the patient's specific HLA (Human Leukocyte Antigen) alleles. Despite their potential, therapeutic challenges include the heterogeneity of neoantigen expression within a tumor and the potential for tumor escape through the loss of MHC expression.

Other names

Tumor-specific antigen-MHC complexNeoepitope-HLA complexPatient-specific neoantigen-MHCpMHC complexTumor-specific neoantigen-HLA complex

Induction of a specific T-cell mediated immune response against tumor cells by presenting unique, mutation-derived peptides in the context of MHC molecules (Sahin & Türeci, Science, 2018).