Mutant KRAS G12A peptide epitope (KRAS G12A)

The mutant KRAS G12A peptide epitope is a tumor-specific neoantigen resulting from a point mutation at codon 12 of the Kirsten rat sarcoma viral oncogene (KRAS) protein, where glycine is replaced by alanine [1.1.2, 1.4.1]. This mutation is a key driver in several malignancies, particularly colorectal and non-small cell lung cancers, where it promotes uncontrolled cell proliferation by maintaining the KRAS protein in a constitutively active, GTP-bound state [1.1.2, 1.1.3]. As a peptide epitope, it is generated through intracellular proteasomal degradation and subsequently presented on the cell surface by Major Histocompatibility Complex (MHC) class I or II molecules [1.2.1, 1.4.4]. This presentation allows the immune system to distinguish malignant cells from healthy ones, making the epitope a high-priority target for immunotherapies such as cancer vaccines and T-cell receptor (TCR)-engineered T-cell therapies [1.2.3, 1.3.2]. For instance, the multi-peptide vaccine ELI-002 (7P formulation) is designed to stimulate T-cell responses against this and other common KRAS mutations [1.3.4]. Therapeutic efficacy is often dependent on the patient's specific Human Leukocyte Antigen (HLA) type, as the G12A peptide must bind effectively to the HLA groove to be recognized by T-cells [1.2.1, 1.4.2]. While small-molecule inhibitors for G12A are still in early development, targeting the peptide epitope offers a way to bypass the "undruggable" nature of the KRAS protein's smooth surface by utilizing the specificity of the adaptive immune response [1.4.4, 1.5.1].

Other names

KRAS G12A neoantigenKRAS G12A mutant peptideKRAS G12A p-HLA complexKirsten rat sarcoma viral oncogene homolog G12A epitope

MHC-restricted T-cell activation, active immunization, adoptive cell transfer