KRAS mutant neoantigen-expressing tumor cells (mKRAS-expressing tumor cells)

KRAS mutant neoantigen-expressing tumor cells are malignant cells that present unique peptide fragments derived from mutated KRAS proteins on their surface via Major Histocompatibility Complex (MHC) molecules [1.2.1, 1.2.3]. KRAS is a proto-oncogene GTPase that functions as a binary switch in signal transduction pathways regulating cell growth and survival [1.1.2]. Mutations at specific hotspots, such as G12D, G12V, and G12C, lead to constitutive activation of the protein, driving uncontrolled proliferation in cancers like pancreatic ductal adenocarcinoma, colorectal cancer, and non-small cell lung cancer [1.2.1, 1.4.1]. Because these mutant peptides are absent in healthy tissues, they serve as highly specific neoantigens that can be recognized by the adaptive immune system [1.2.4, 1.3.3]. Therapeutic strategies targeting these cells include direct small-molecule inhibitors like sotorasib and adagrasib, as well as TCR-engineered T-cell therapies and cancer vaccines like mRNA-5671 [1.2.4, 1.3.1]. These immunological approaches aim to achieve high tumor specificity by leveraging the immune system's ability to detect intracellular mutations presented as peptide-MHC complexes on the cell surface [1.2.5, 1.3.2]. However, challenges such as HLA loss and the immunosuppressive tumor microenvironment remain significant hurdles for effective treatment [1.3.1, 1.4.4].

Other names

KRAS-mutant cancer cellsKRAS neoantigen-positive tumor cellsmKRAS-expressing tumor cellsKRAS pMHC-expressing cellsMutant KRAS-driven tumor cells

T-cell mediated cytotoxicity, direct inhibition of mutant KRAS GTPase activity, redirected T-cell activation via bispecific TCR-CD3 engagement, and induction of adaptive immune response via neoantigen vaccination [1.2.4, 1.2.5, 1.3.1].