Patient-specific neoantigen-major histocompatibility complex (NeoAg-MHC)

Patient-specific neoantigen-major histocompatibility complex (NeoAg-MHC) refers to the presentation of unique, mutation-derived peptides on the surface of tumor cells and professional antigen-presenting cells (APCs). These neoantigens arise from somatic mutations—such as single nucleotide variants, insertions/deletions, or chromosomal rearrangements—that are entirely absent from the host's normal genome, making them ideal targets for highly specific immunotherapy (Schumacher & Schreiber, Science 2015). When these peptides are processed and loaded onto MHC Class I or Class II molecules, they serve as "non-self" signals that can be recognized by the T-cell receptors (TCRs) of CD8+ and CD4+ T cells, respectively (Sahin & Türeci, Science 2018). Therapeutic strategies targeting these complexes include personalized mRNA or peptide vaccines designed to prime the immune system, as well as adoptive cell therapies using TCR-engineered T cells (Blass & Ott, Nature Reviews Clinical Oncology 2021). Because neoantigens are unique to each patient's tumor, these treatments represent a cornerstone of precision oncology, aiming to minimize off-target toxicity while maximizing anti-tumor efficacy. However, challenges remain regarding the accurate prediction of which mutations will produce immunogenic peptides and the potential for tumors to escape immune surveillance by downregulating MHC expression (Hu et al., Nature Reviews Cancer 2021).

Other names

Tumor-specific neoantigen-HLA complexNeoepitope-MHC complexMutation-derived antigen-MHC complexPersonalized neoantigen-MHCpMHC complex

Induction of de novo T-cell responses and expansion of pre-existing neoantigen-specific T-cell populations that recognize the peptide-MHC complex on tumor cells to trigger cytotoxic cell death.