Kirsten rat sarcoma virus oncogene mutant peptide antigen (KRAS mutant peptide antigen)

The "KRAS protein mutant peptide antigen" refers to short amino acid sequences derived from mutated forms of the Kirsten rat sarcoma virus oncogene product—most notably those containing common oncogenic mutations such as G12V. These mutated peptides are presented by major histocompatibility complex class I molecules on the surface of cancer cells and can be recognized as neoantigens by cytotoxic T lymphocytes. This property makes them attractive targets for immunotherapies such as adoptive transfer of engineered T cell receptors with specificity for these epitopes. Additionally, recent research has shown that synthetic amyloidogenic peptides can exploit intrinsic vulnerabilities in the structure of mutant KRAS proteins—inducing their misfolding and functional inactivation—which represents an alternative therapeutic strategy beyond conventional small molecule inhibitors. The use of these antigens is primarily relevant in cancers driven by activating mutations in the KRAS gene; however, safety concerns remain regarding potential cross-reactivity with normal human proteins when using highly specific immune-based therapies.[1][2][3]

Other names

Mutant KRAS neoantigenKRAS G12V peptide antigenKRAS mutant epitopeOncogenic KRAS peptide

Immune recognition by engineered T cell receptors specific for the mutated peptide presented on HLA class I molecules[2] Induction of misfolding and aggregation to inactivate the oncoprotein using synthetic peptides[1]