Mutant Kirsten rat sarcoma viral oncogene homolog (KRAS) neoantigen peptides (Mutant KRAS neoantigens)

Mutant KRAS neoantigen peptides are short amino acid sequences derived from the mutated Kirsten rat sarcoma viral oncogene homolog (KRAS) protein, which is a central driver in many aggressive malignancies including pancreatic, colorectal, and lung cancers (PubMed: 32103171). These peptides arise from specific point mutations—most commonly at codons 12, 13, or 61—and are processed and presented on the surface of cancer cells by Human Leukocyte Antigen (HLA) molecules (NIH: PMC7045352). Because these mutant sequences are absent in healthy tissues, they serve as highly specific non-self targets for the immune system, making them ideal candidates for precision immunotherapies (Nature: 10.1038/s41586-021-04335-5). Therapeutic approaches targeting these neoantigens include cancer vaccines (peptide, DNA, or mRNA-based) and adoptive T-cell therapies, such as TCR-engineered T cells (TCR-T), which are designed to recognize the peptide-HLA complex (PubMed: 35613031). By stimulating a robust CD8+ and CD4+ T-cell response, these therapies aim to selectively eliminate KRAS-mutant tumor cells while sparing normal tissue. Despite their potential, challenges remain regarding the diversity of HLA alleles across the population and the ability of tumors to evade detection through the loss of antigen presentation machinery (Science: 10.1126/science.abc1675). Current clinical trials are evaluating these neoantigens as targets to overcome the historical undruggability of KRAS mutations (PubMed: 34019806).

Other names

KRAS mutant peptidesKRAS-derived neoantigensmKRAS neoantigensMutant KRAS-derived HLA-presented peptidesKRAS G12D/G12V/G12C neoantigens

Induction of mutation-specific T-cell mediated cytotoxicity where vaccines or adoptive cell therapies prime the immune system to recognize and eliminate tumor cells presenting mutant KRAS peptide fragments on MHC/HLA molecules (PubMed: 35613031).