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

KRAS mutant neoantigen peptides are short amino acid sequences derived from the mutated Kirsten rat sarcoma virus oncogene homolog protein, specifically involving substitutions at codons 12 and 13. These mutations, such as G12C, G12D, G12V, and G13D, are highly prevalent in solid tumors including pancreatic, colorectal, and lung cancers [1, 2]. Because these sequences are unique to tumor cells, they serve as highly specific neoantigens that can be recognized by the immune system when presented on the cell surface by human leukocyte antigen (HLA) molecules [3]. Therapeutic strategies targeting these peptides include cancer vaccines, which aim to prime the patient's own T-cells, and adoptive T-cell therapies (TCR-T), which involve engineering T-cells to express receptors specific to these KRAS-mutant epitopes [4, 5]. Unlike direct KRAS inhibitors that bind the protein's pocket, neoantigen-directed therapies leverage the cellular immune response to achieve tumor-specific lysis [3, 5]. This approach is particularly valuable for targeting mutations like G12D that have historically been difficult to target with small molecules [2, 5]. References: [1] Prior IA, et al. (2020) Nat Rev Cancer; [2] Simanshu DK, et al. (2017) Cell; [3] Pant S, et al. (2024) Nat Med; [4] ClinicalTrials.gov NCT03948178; [5] Leidner R, et al. (2022) N Engl J Med.

Other names

KRAS neoepitopesKRAS mutant peptidesKRAS G12/G13 mutant antigensMutant KRAS-derived peptides

Induction of a mutation-specific T-cell response (CD8+ cytotoxic and CD4+ helper T-cells) that recognizes KRAS-mutant peptides presented on MHC/HLA molecules, leading to the selective destruction of tumor cells [3, 5].