Mutated GNAS neoantigen peptide-MHC complex (GNAS neoantigen-MHC)

Mutated GNAS neoantigen peptides presented on the Major Histocompatibility Complex (MHC) represent a highly specific class of tumor-specific antigens derived from somatic mutations in the GNAS gene. GNAS encodes the alpha subunit of the stimulatory G protein (Gs-alpha), and hotspot mutations—most commonly R201H and R201C—result in constitutive activation of adenylate cyclase and elevated cAMP levels, driving oncogenesis in specific malignancies like pancreatic and appendiceal cancers (Source: PubMed, PMID: 30217936). Because these mutations are absent in healthy tissue, the resulting peptides presented on the cell surface by MHC molecules serve as ideal targets for precision immunotherapy, including TCR-engineered T-cells and neoantigen vaccines (Source: NIH, NCI). Therapeutic strategies focus on identifying the specific HLA alleles (such as HLA-A*02:01) that can effectively present these mutated sequences to the immune system. Current clinical efforts, such as the ELI-002 vaccine, aim to prime the patient's immune system to recognize these GNAS-derived neoepitopes to eliminate residual disease and prevent relapse (Source: Elicio Therapeutics). This target is particularly valuable in 'undruggable' cancers where direct small-molecule inhibition of the mutated protein has proven difficult.

Other names

GNAS R201H neoantigenGNAS R201C neoantigenGNAS-derived neoepitopeMutated GNAS peptide-HLA complexGuanine nucleotide-binding protein G(s) subunit alpha neoantigen

Targeting of the specific mutated peptide sequence presented by the Major Histocompatibility Complex (MHC) via T-cell receptors (TCRs) or vaccine-induced immune responses to trigger selective lysis of tumor cells.