IDO1
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.
Overview
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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
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.
- 3 · How drugs use it
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.
External identifiers
Biology
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.
- Tumour cells and myeloid cells of the tumour microenvironment
- Melanoma and head and neck cancer (IO102-IO103); melanoma (epacadostat)
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.
Notes
top- Prevalence not recorded in this wave: HGNC and UniProt carry no positivity rates and no other source was consulted.
Latest papers
topQuery 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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