Mutant Kirsten rat sarcoma virus oncogene homolog peptide–Major histocompatibility complex (KRAS-MHC complex)

Mutant KRAS peptide–MHC complexes are neoantigens presented on the surface of tumor cells, resulting from the intracellular processing of mutated KRAS proteins. These complexes consist of a mutant KRAS-derived peptide (such as G12D, G12V, or G12C) bound to a Major Histocompatibility Complex (MHC) molecule, typically HLA Class I. Because these mutant peptides are absent in normal tissues, the complexes serve as highly specific targets for the immune system, allowing for the selective destruction of malignant cells. Therapeutic strategies targeting these complexes include T-cell receptor (TCR)-engineered T cells (TCR-T) and TCR-mimic (TCRm) bispecific antibodies that recognize the unique peptide-HLA interface to induce T-cell mediated tumor cell lysis. This approach effectively bypasses the historical difficulty of directly inhibiting the KRAS protein with small molecules by utilizing the cell's natural antigen presentation pathway. These therapies are currently being evaluated in clinical trials for KRAS-mutant solid tumors, including pancreatic, colorectal, and lung cancers, where they aim to overcome resistance to traditional targeted therapies.

Other names

Mutant KRAS neoantigen-MHC complexKRAS neoepitope-HLA complexHaptenated KRAS-MHC complexp-HLA complexKRAS-HLA complex