Patient-specific neoantigen–Major Histocompatibility Complex (MHC) complex (NeoAg-MHC)

Patient-specific neoantigen–Major Histocompatibility Complex (MHC) complexes are personalized molecular targets formed by the binding of tumor-specific mutant peptides to an individual's own HLA molecules (Schumacher & Schreiber, 2015, Science). These neoantigens arise from non-synonymous somatic mutations within the tumor genome and are absent from normal tissues, making them ideal targets for high-precision immunotherapy (Ott et al., 2017, Nature). In the context of dendritic cell (DC) vaccines, these complexes are generated by loading autologous DCs with synthetic neoantigen peptides in vitro. Once administered, these peptide-pulsed DCs present the neoantigen-MHC complexes to naive T cells, initiating a potent and specific cytotoxic T lymphocyte (CTL) response against the tumor (Carreno et al., 2015, Science). This therapeutic approach leverages the natural role of dendritic cells as professional antigen-presenting cells to overcome immune tolerance often found in the tumor microenvironment (Banchereau & Steinman, 1998, Nature). By targeting unique mutations, these complexes minimize the risk of off-target autoimmune damage while maximizing the breadth of the anti-tumor immune repertoire (Sahin et al., 2017, Nature).

Other names

Neoantigen-HLA complexTumor-specific neoantigen-MHC complexPersonalized neoepitope-MHC complexNeoantigen-pulsed dendritic cell vaccine target

Induction of tumor-specific T-cell responses through the presentation of somatic mutation-derived peptides on MHC molecules to T-cell receptors (TCRs).