Tumor-specific neoantigen peptides derived from KRAS, TP53, Beta-catenin, and BRAF mutations (KRAS/TP53/CTNNB1/BRAF Neoantigens)

Tumor-specific neoantigen peptides derived from mutations in KRAS, TP53, Beta-catenin (CTNNB1), and BRAF represent a class of highly specific therapeutic targets for cancer immunotherapy [PubMed: 31534203]. These peptides arise from somatic hotspot mutations that are common across various malignancies but absent in healthy tissues, providing a high therapeutic index with minimal risk of central tolerance or autoimmunity [Nature: 10.1038/s41591-018-0048-2]. When these mutated proteins are processed by the proteasome, the resulting neoantigenic peptides are presented on the cell surface by Major Histocompatibility Complex (MHC) molecules for recognition by CD8+ and CD4+ T cells [PubMed: 30104371]. Therapeutic strategies, such as mRNA vaccines (e.g., mRNA-5671), peptide vaccines, and adoptive T-cell receptor (TCR) therapies, aim to prime or engineer the immune system to recognize these specific peptide-MHC complexes [NEJM: 10.1056/NEJMoa2119662]. Because these mutations are frequent drivers in colorectal, pancreatic, and lung cancers, targeting these shared neoantigens allows for the development of off-the-shelf immunotherapies for large patient populations [PubMed: 35653551]. However, the efficacy of these treatments is highly dependent on the patient's specific HLA genotype and the tumor's ability to maintain antigen presentation machinery [PubMed: 29074444].

Other names

Shared neoantigensHotspot mutation-derived neoantigensPublic neoantigensMutation-derived tumor antigensKRAS/TP53/CTNNB1/BRAF shared antigens

Induction of a specific T-cell mediated immune response against tumor cells presenting mutated peptide fragments on MHC molecules.