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IDO1 is an enzyme tumours use to burn up tryptophan, starving T cells and producing by-products that switch them off. Epacadostat blocked it but its programme ended in failure; the IO102-IO103 vaccine instead teaches T cells to attack the IDO1-expressing cells themselves.
IDO1 (chromosome 8p11.21) catalyses the first, rate-limiting step of tryptophan catabolism along the kynurenine pathway; the tryptophan shortage stops T lymphocytes dividing and the catabolites induce T-cell apoptosis and regulatory T-cell differentiation, so the enzyme maintains peripheral tolerance, protects the fetus from maternal rejection, limits intracellular pathogens and suppresses anti-tumour immunity (UniProt P14902). In OnCo, IDO1 is the target of epacadostat, a selective reversible enzyme inhibitor recorded as a negative programme in melanoma, and one of the two antigens (with PD-L1) of the IO102-IO103 peptide vaccine in phase 3 for melanoma and head and neck cancer.
In plain words · IDO1 is an enzyme tumours use to burn up tryptophan, starving T cells and producing by-products that switch them off. Epacadostat blocked it but its programme ended in failure; the IO102-IO103 vaccine instead teaches T cells to attack the IDO1-expressing cells themselves.
IDO1 is an enzyme tumours use to burn up tryptophan, starving T cells and producing by-products that switch them off. Epacadostat blocked it but its programme ended in failure; the IO102-IO103 vaccine instead teaches T cells to attack the IDO1-expressing cells themselves.
The two corpus approaches differ in kind: epacadostat blocked the enzyme's chemistry, while IO102-IO103 raises T cells against cells that express IDO1 or PD-L1 in the tumour microenvironment, turning the suppressive cells themselves into targets.
2 products aim at IDO1: vaccines and small molecules. Inhibitors are shaped to fit the enzyme's active site so the reaction the cancer relies on stops.
Immune or microenvironment target: its medicines act on immune, stromal or bone cells rather than on the tumour cell (drug mechanisms in the corpus). HPA IDO1: RNA tissue enhanced (lymphoid tissue 55 nTPM, placenta 104 nTPM); blood lineage lineage enriched (granulocytes 466 nTPM); high antibody staining in 4 normal tissues; highest cancer staining cervical cancer (3 of 12 high). Distribution: 2 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Skin cancer (all types), Head and neck squamous cell carcinoma); Open Targets associates it with 0 specific cancer types at or above 0.5. (Rule 1 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas IDO1 tissue; UniProt P14902; Open Targets ENSG00000131203 associations
First described 1990. Earliest sequence paper UniProt cites for the protein: Dai et al, Biochem. Biophys. Res. Commun, 1990, "Molecular cloning, sequencing and expression of human interferon-gamma-inducible indoleamine 2,3-dioxygenase cDNA". Source.
The two corpus approaches differ in kind: epacadostat blocked the enzyme's chemistry, while IO102-IO103 raises T cells against cells that express IDO1 or PD-L1 in the tumour microenvironment, turning the suppressive cells themselves into targets.
RNA: tissue enhanced (lymphoid tissue 55 nTPM, placenta 104 nTPM), detected in many normal tissues. Blood: lineage enriched (granulocytes 466 nTPM).
Medium: Appendix, Rectum, Spleen, Tonsil.
Medium only: carcinoid, head and neck cancer, melanoma, prostate cancer.
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
An enzyme blocker meant to stop tumours starving T cells of tryptophan. Its 2018 phase 3 failure ended an entire class overnight.
IO102-IO103 is an experimental peptide (immunotherapeutic vaccine) from IO Biotech in phase 3 trials for melanoma and head and neck squamous cell carcinoma, aimed at PD-L1.
Query for this target: (TITLE:"IDO1" OR ABSTRACT:"IDO1" OR TITLE:"IDO" OR ABSTRACT:"IDO" OR TITLE:"INDO" OR ABSTRACT:"INDO" OR TITLE:"indoleamine 2,3-dioxygenase 1" OR ABSTRACT:"indoleamine 2,3-dioxygenase 1") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about IDO1, not a curated reading list.
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