Mutant RAS peptide-HLA class I complex (Mutant RAS-HLA-I)

Mutant RAS peptide-HLA class I complexes are neoantigens formed when intracellular mutant RAS proteins (such as KRAS G12D, G12V, or G12C) are degraded into short peptides and presented on the cell surface by Human Leukocyte Antigen (HLA) class I molecules (1.1.1, 1.3.3). These complexes are highly specific to tumor cells, as the mutant peptides are absent in normal tissues, making them ideal targets for precision immunotherapy (1.3.2, 1.4.1). RAS mutations are prevalent in approximately 20-25% of all human cancers, including the majority of pancreatic, colorectal, and lung adenocarcinomas (1.1.1, 1.3.1). Therapeutic approaches targeting these complexes include T-cell receptor-engineered T-cell (TCR-T) therapies, bispecific T-cell engagers (BiTEs), and TCR-mimic (TCRm) antibodies, which are designed to recognize the specific peptide-HLA configuration (1.2.1, 1.3.5). By redirecting the immune system to recognize these historically "un-druggable" intracellular drivers, these therapies aim to induce potent and selective tumor cell lysis (1.2.2, 1.4.4). However, clinical success is often challenged by the low surface density of the complexes and the potential for tumor escape through the downregulation of HLA expression or antigen processing machinery (1.1.4, 1.4.4).

Other names

Mutant RAS-derived peptides presented by HLA class I moleculesRAS neoantigen-HLA complexMutant RAS-MHC class I complexRAS peptide-MHC complexMutant RAS pHLA

T-cell redirection and mediated cytotoxicity through specific recognition of the mutant peptide-HLA complex.