Mutant Kirsten rat sarcoma virus oncogene homolog neoantigen (Mutant KRAS neoantigen) (Mutant KRAS neoantigen)

Mutant KRAS neoantigens are specific peptide fragments derived from oncogenic mutations in the Kirsten rat sarcoma virus oncogene homolog (KRAS) protein, which are presented on the surface of tumor cells by Human Leukocyte Antigen (HLA) molecules (UniProt P01116). KRAS mutations, particularly at codon 12 (e.g., G12D, G12V, G12C), are driver events in a significant proportion of human malignancies, including over 90% of pancreatic ductal adenocarcinomas and approximately 40% of colorectal cancers (Bear et al., 2020). Because these mutations are absent in normal tissues, the resulting neoantigens are highly tumor-specific, making them ideal targets for immunotherapy while minimizing the risk of off-tumor toxicity. Therapeutic approaches targeting these neoantigens include the use of T-cell receptor (TCR) engineered T cells (TCR-T) and neoantigen vaccines designed to elicit or expand a Mutant KRAS neoantigen-specific T-cell response (Leidner et al., 2022; Pant et al., 2023). These therapies rely on the precise recognition of the mutant peptide-HLA complex by T cells, which subsequently execute a cytotoxic program to eliminate the cancer cells (Tran et al., 2016). Clinical trials have demonstrated the potential for durable objective responses in patients with advanced solid tumors, although challenges such as HLA loss and the immunosuppressive tumor microenvironment remain significant hurdles.

Other names

KRAS mutation-derived neoantigenKRAS G12D neoantigenKRAS G12V neoantigenMutant KRAS peptide-HLA complexmKRAS neoantigen

T-cell receptor (TCR) mediated recognition of mutant KRAS-derived peptides presented on Major Histocompatibility Complex (MHC) molecules, leading to the activation of cytotoxic T-lymphocytes and subsequent lysis of tumor cells (Tran et al., 2016; Leidner et al., 2022).