T-cell receptor recognizing Ornithine decarboxylase 1–Major Histocompatibility Complex Class I complex (TCR-ODC1-MHC I)

T-cell receptors (TCRs) recognizing Ornithine decarboxylase 1 (ODC1) peptides in complex with Major Histocompatibility Complex Class I (MHC I) are specialized immune receptors used in adoptive cell therapy. ODC1 is a rate-limiting enzyme in polyamine biosynthesis that is frequently overexpressed in various malignancies, particularly MYCN-amplified neuroblastoma and certain colorectal cancers (UniProt P11926; Singh et al., 2021). These TCRs are typically engineered into a patient's own T cells (TCR-T therapy) to enable the recognition of ODC1-derived epitopes, such as the HLA-A*02:01-restricted peptide ODC1_422-431 (ILVGDVGAV). Upon binding to the pMHC complex on the tumor cell surface, the TCR initiates a signaling cascade that leads to the targeted destruction of the cancer cell (Science Translational Medicine, 2021). This approach leverages the metabolic dependency of certain tumors on high polyamine levels, which results in the presentation of ODC1-derived antigens that are relatively rare on healthy cells. Clinical development focuses on ensuring high specificity to avoid off-target effects on healthy tissues that maintain basal polyamine metabolism.

Other names

ODC1-specific T-cell receptorTCR recognizing ODC1-derived peptideOrnithine decarboxylase 1-specific TCRTCR-ODC1

Recognition of the ODC1 peptide-MHC I complex on tumor cells by engineered T-cells, leading to immunological synapse formation and cytotoxic T-lymphocyte (CTL) mediated lysis.