ADP-dependent glucokinase neoantigen peptide–MHC class I complex (ADPGK neoantigen–MHC-I)

The ADP-dependent glucokinase (ADPGK) neoantigen peptide–MHC class I complex is a highly specific tumor target consisting of a mutated ADPGK peptide fragment bound to a Major Histocompatibility Complex (MHC) class I molecule. This complex is primarily recognized in the context of the V429M mutation, which creates a novel epitope that is presented on the surface of cancer cells, most notably in the MC38 murine colon adenocarcinoma model (Yadav et al., Nature, 2014; PubMed: 25428506). As a neoantigen, it is not expressed in normal tissues, making it an exceptional candidate for immunotherapy with minimal risk of off-target toxicity. Therapeutic approaches targeting this complex include the development of personalized peptide or mRNA vaccines and the engineering of T-cell receptor (TCR) therapies that specifically bind the peptide-MHC interface (Castle et al., Cancer Research, 2012; PubMed: 22237626). The biological function of this complex is to serve as a signal for CD8+ T-cell activation, leading to the targeted destruction of the tumor cell. Despite its potential, the clinical utility of targeting this complex can be limited by immune evasion mechanisms such as the loss of MHC expression or the emergence of antigen-negative tumor clones (Schumacher & Schreiber, Science, 2015; PubMed: 25838375).

Other names

Mutated ADPGK peptide-MHC complexADPGK V429M neoantigenH-2Db/ADPGK(V429M) complexADP-dependent glucokinase neoepitopeMutant ADPGK-MHC complex

Recognition of the specific mutated peptide-MHC interface by the T-cell receptor (TCR) of CD8+ cytotoxic T lymphocytes, triggering the release of perforin and granzymes to induce apoptosis in the tumor cell (Yadav et al., Nature, 2014).