Mutant Kirsten rat sarcoma virus oncogene homolog (KRAS) neoantigenic peptide-Major Histocompatibility Complex class I (MHC I) complex (Mutant KRAS-MHC I complex)

The Mutant KRAS neoantigenic peptide-MHC class I complex is a tumor-specific target formed when intracellular mutant KRAS proteins are processed by the proteasome and presented on the cell surface by Major Histocompatibility Complex (MHC) class I molecules (1.1.1, 1.2.1). These complexes are considered "public" neoantigens because specific mutations like G12D, G12V, and G12C occur frequently across many patients with pancreatic, colorectal, and lung cancers (1.2.2, 1.4.2). Because these peptides are derived from somatic mutations, they are absent in normal tissues, providing a high degree of therapeutic selectivity for the immune system (1.2.3, 1.4.1). Therapeutic strategies targeting these complexes include TCR-engineered T-cell (TCR-T) therapies, neoantigen vaccines, and TCR-mimic (TCRm) bispecific antibodies (1.2.4, 1.5.3). A novel approach involves using covalent KRAS inhibitors to create drug-modified "haptenated" peptides that are presented on MHC I, which can then be targeted by specialized bispecific T-cell engagers to overcome drug resistance (1.3.1, 1.3.5). However, challenges remain due to the low surface density of these complexes and the requirement for precise matching of the patient's HLA allele with the therapeutic agent (1.1.3, 1.4.4).

Other names

KRAS neoantigen-HLA complexMutant KRAS-HLA-I complexKRAS G12D/G12V/G12C neoantigenpMHC complexKRAS-mutant peptide-HLA complexHaptenated KRAS-MHC complex

T-cell receptor (TCR) binding, Immune activation, Cytotoxic T-lymphocyte (CTL) mediated killing, Hapten-based immunotherapy