Neuroblastoma RAS viral oncogene homolog (NRAS) neoantigen-derived peptide (NRAS neoantigen)

NRAS neoantigen-derived peptides are short amino acid sequences resulting from somatic mutations in the NRAS gene, a member of the RAS GTPase family (UniProt P01111). These mutations, most frequently occurring at codons 12, 13, and 61, lead to the production of non-self proteins that can be processed and presented by Major Histocompatibility Complex (MHC) molecules on the surface of cancer cells (Schumacher & Schreiber, 2015, Science). Because these peptides are unique to the tumor and absent in healthy tissues, they serve as highly specific targets for immunotherapy, including therapeutic cancer vaccines and T-cell receptor (TCR) engineered T-cell therapies (NCT05261269). Targeting NRAS neoantigens aims to stimulate the patient's immune system to recognize and eliminate malignant cells while minimizing damage to normal cells. This approach is particularly relevant in cancers with high NRAS mutation frequencies, such as cutaneous melanoma (approx. 20%) and certain leukemias (Hodis et al., 2012, Cell). Drugs interacting with these targets, such as personalized mRNA vaccines (e.g., mRNA-4157), work by priming the immune system to identify these specific mutant sequences, thereby driving a targeted anti-tumor response.

Other names

NRAS mutant peptideNRAS-derived neoepitopeMutated NRAS peptideNRAS Q61 neoantigenNRAS G12 neoantigen

Induction of tumor-specific T-cell responses (CD8+ and CD4+) against cells presenting mutated NRAS peptides on MHC molecules.