Ornithine decarboxylase 1-derived neoantigen peptide–HLA class I complex (ODC1 neoantigen–HLA-I complex)

The ODC1-derived neoantigen peptide–HLA class I complex is a tumor-specific target formed by the presentation of mutated ornithine decarboxylase 1 (ODC1) fragments on the cell surface via Human Leukocyte Antigen (HLA) class I molecules. ODC1 is a critical rate-limiting enzyme in the polyamine biosynthesis pathway, and its dysregulation is a hallmark of many hyperproliferative tissues and cancers, including glioblastoma and renal cell carcinoma (UniProt, NIH). Somatic mutations in ODC1, such as the Q129L mutation identified in preclinical glioma models, generate novel peptide sequences known as neoepitopes that are absent in healthy tissues (NIH, ResearchGate). These neoepitopes are processed and presented by specific HLA alleles, where they can be recognized by the T-cell receptors (TCRs) of cytotoxic CD8+ T cells to trigger an anti-tumor immune response (NIH, Frontiers). This complex is a primary focus for the development of personalized cancer immunotherapies, including synthetic long peptide (SLP) vaccines like IMA901 and adoptive TCR-T cell therapies (Frontiers, ClinicalTrials.gov). By targeting the unique mutated sequence, these therapies aim to achieve high specificity and minimize off-target effects on normal cells expressing wild-type ODC1. However, therapeutic success depends on the presence of the specific mutation and the corresponding HLA allele, as well as overcoming potential immune evasion mechanisms like HLA downregulation (NIH).

Other names

ODC1-mutant peptide-MHC complexODC1 neoepitope-HLA complexOdc1 Q129L-H-2Db complexODC1-derived pHLAOrnithine decarboxylase 1 neoantigen

T-cell mediated cytotoxicity