Kirsten rat sarcoma virus oncogene homolog mutant neoantigen peptides (KRAS mutant neoantigens)

Kirsten rat sarcoma virus oncogene homolog (KRAS) mutant neoantigen peptides are short fragments of the KRAS protein containing specific oncogenic mutations, such as G12D, G12V, or G12C, which are presented on the surface of cancer cells by Human Leukocyte Antigen (HLA) molecules [1, 2]. These peptides are considered "neoantigens" because they are not present in the normal human proteome, making them ideal targets for highly specific cancer immunotherapies that spare healthy tissues [2, 3]. In diseases like pancreatic ductal adenocarcinoma and colorectal cancer, where KRAS mutations are nearly ubiquitous, these neoantigens serve as critical focal points for the development of therapeutic vaccines and adoptive T-cell therapies [1, 4]. Vaccines, including peptide-based and mRNA-based platforms, aim to stimulate the patient's own immune system to recognize and destroy cells displaying these mutant sequences [5]. Alternatively, engineered T-cell receptor (TCR) therapies involve the infusion of T-cells specifically programmed to bind the KRAS peptide-MHC complex, a strategy that has shown clinical efficacy in treating advanced solid tumors [4, 6]. Despite their promise, the effectiveness of targeting KRAS neoantigens can be limited by the diversity of HLA alleles in the population and the ability of tumors to downregulate antigen presentation machinery to evade immune detection [3, 6].

Other names

KRAS neoepitopesMutant KRAS peptidesKRAS-derived neoantigensmKRAS peptides

Induction of a mutation-specific T-cell immune response through vaccination or adoptive transfer of T-cells expressing receptors specific for the mutant KRAS peptide-HLA complex.