Mutant Kirsten rat sarcoma virus oncogene homolog G12S peptide epitope (KRAS G12S peptide)

The Mutant KRAS G12S peptide epitope is a neoantigen derived from the Kirsten rat sarcoma virus oncogene homolog (KRAS) protein, specifically featuring a glycine-to-serine substitution at position 12 [1]. KRAS is a member of the Ras GTPase family that functions as a molecular switch, cycling between active GTP-bound and inactive GDP-bound states to regulate downstream signaling pathways like MAPK/ERK and PI3K/AKT, which govern cell proliferation and survival [1, 2]. The G12S mutation impairs the protein's ability to hydrolyze GTP, resulting in constitutive activation that drives the development of various cancers, particularly non-small cell lung cancer and colorectal cancer [2, 4]. As a peptide epitope, this mutant sequence is processed by the proteasome and presented on the cell surface by Human Leukocyte Antigen (HLA) molecules, where it can be recognized by the T-cell receptor (TCR) of cytotoxic T cells [3]. This makes the G12S epitope a highly specific target for immunotherapies, such as the amphiphile vaccine ELI-002, which aims to stimulate a robust, mutation-specific immune response against tumor cells while sparing healthy tissue [3, 5]. Therapeutic challenges include the potential for tumor antigen escape through HLA downregulation and the requirement for specific HLA alleles to present the peptide effectively to the immune system [4, 5]. Sources: [1] UniProt Consortium. "KRAS - GTPase KRas precursor." UniProtKB - P01116. [2] National Cancer Institute. "KRAS Gene." NCI Dictionary of Genetics Terms. [3] Elicio Therapeutics. "ELI-002: An Investigational KRAS-Targeted Amphiphile Cancer Vaccine." [4] Huang, L., et al. (2021). "KRAS mutations: from undruggable to druggable." Signal Transduction and Targeted Therapy. [5] ClinicalTrials.gov. "A Study of ELI-002 in Subjects With KRAS Mutated Solid Tumors (AMPLIFY-201)."

Other names

KRAS G12S neoantigenKRAS G12S mutant peptideG12S KRAS epitopeKRAS G12S peptide antigen

Induction of mutation-specific T-cell responses through the presentation of the mutant peptide on HLA molecules, leading to the recognition and lysis of KRAS G12S-expressing tumor cells.