oleclumab   Click here for help

GtoPdb Ligand ID: 9596

Synonyms: MEDI 9447 | MEDI-9447
Immunopharmacology Ligand
Compound class: Antibody
Comment: Oleclumab (MEDI9447) is a monoclonal antibody targeting the ecto-5'-nucleotidase (CD73), which is being investigated for oncology use [1-2]. Functional studies show that MEDI9447 is a high affinity antagonistic mAb, showing non-competitive inhibition of CD73 hydrolysis of AMP[1]. Two modes of action are suggested: prevention of steric conformational change required for catalytic active state, and inter-CD73 dimer cross-linking.
Annotated peptide sequences for this antibody are available from its IMGT/mAb-DB record.
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No information available.
Summary of Clinical Use Click here for help
Oleclumab (MEDI9447) is in Phase 1 clinical trial ± durvalumab, an approved anti-PD-L1 immuno-oncology agent vs. select advanced solid tumours- see NCT02503774.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Adenosine signaling through A2a receptors on CD4+ and CD8+ T lymphocytes and natural killer cells leads to the suppression of effector functions. Cancer cells expoloit this mechanism by upregulating CD73 expression which elevates extracellular adenosine levels in the tumour microenvironment and inhibits immunosurveillance against the tumour cells. Inhibiting CD73 is recognised as a possible pharmacological intervention to de-repress CD73's anti-tumour immune effect.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT02503774 MEDI9447 Alone and in Combination With MEDI4736 in Adult Subjects With Select Advanced Solid Tumors Phase 1 Interventional MedImmune LLC