ArticlemAbs2016
Inhibition of CD73 AMP hydrolysis by a therapeutic antibody with a dual, non-competitive mechanism of action.
Article in mAbs, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
61 citing papers in PubMed, 108 citations in OpenAlex.
- Durvalumab plus Paclitaxel, with or without Capivasertib or Oleclumab, in Patients with Locally Advanced/Metastatic Triple-Negative Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- A Phase Ib/II Randomized Clinical Trial of Oleclumab with or without Durvalumab plus Chemotherapy in Patients with Metastatic Pancreatic Ductal Adenocarcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Trial
- COLUMBIA-1: a randomised study of durvalumab plus oleclumab in combination with chemotherapy and bevacizumab in metastatic microsatellite-stable colorectal cancer.British journal of cancer · 2024Trial
- Article
- Sym024 Interacts with a Unique Epitope on the CD73 Homodimer, Favoring Effective Bivalent Binding to Improve Anti-PD-1 Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Dual-mechanism anti-CD73 antibodies CR201 and CR202 targeting distinct domains for cancer immunotherapy.Frontiers in immunology · 2026Article
- CD39 and CD73: biological functions, diseases and therapy.Molecular biomedicine · 2025Review
- An antibody cocktail targeting two different CD73 epitopes enhances enzyme inhibition and tumor control.Nature communications · 2024Article
- The Adenosinergic Pathway in Non-Small Cell Lung Cancer.Cancers · 2024Review
- Multiparatopic antibodies induce targeted downregulation of programmed death-ligand 1.Cell chemical biology · 2024Article
- Posttranslational protein modifications as gatekeepers of cancer immunogenicity.The Journal of clinical investigation · 2024Article
- Pharmacological suppression of the OTUD4/CD73 proteolytic axis revives antitumor immunity against immune-suppressive breast cancers.The Journal of clinical investigation · 2024Article
- PACIFIC-9: Phase III trial of durvalumab + oleclumab or monalizumab in unresectable stage III non-small-cell lung cancer.Future oncology (London, England) · 2024Article
- CD73 deficiency does not aggravate angiotensin II-induced aortic inflammation in mice.Scientific reports · 2023Article
- Anti-inflammatory potency of novel ecto-5'-nucleotidase/CD73 inhibitors in astrocyte culture model of neuroinflammation.European journal of pharmacology · 2023Article
- The Clinical Significance of CD73 in Cancer.International journal of molecular sciences · 2023Review
- First-in-human study of oleclumab, a potent, selective anti-CD73 monoclonal antibody, alone or in combination with durvalumab in patients with advanced solid tumors.Cancer immunology, immunotherapy : CII · 2023Article
- Targeting Cancer Metabolism to Improve Outcomes with Immune Checkpoint Inhibitors.Journal of immunotherapy and precision oncology · 2023Review
- Tumor intrinsic and extrinsic functions of CD73 and the adenosine pathway in lung cancer.Frontiers in immunology · 2023Review
- Safety, tolerability, pharmacokinetics, and antitumour activity of oleclumab in Japanese patients with advanced solid malignancies: a phase I, open-label study.International journal of clinical oncology · 2022Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CD73 (ecto-5'-nucleotidase) has recently been established as a promising immuno-oncology target. Given its role in activating purinergic signaling pathways to elicit immune suppression, antagonizing CD73 (i.e., releasing the brake) offers a complimentary pathway to inducing anti-tumor immune responses. Here, we describe the mechanistic activity of a new clinical therapeutic, MEDI9447, a human monoclonal antibody that non-competitively inhibits CD73 activity. Epitope mapping, structural, and mechanistic studies revealed that MEDI9447 antagonizes CD73 through dual mechanisms of inter-CD73 dimer crosslinking and/or steric blocking that prevent CD73 from adopting a catalytically active conformation. To our knowledge, this is the first report of an antibody that inhibits an enzyme's function through 2 distinct modes of action. These results provide a finely mapped epitope that can be targeted for selective, potent, and non-competitive inhibition of CD73, as well as establish a strategy for inhibiting enzymes that function in both membrane-bound and soluble states.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.