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CD73 is an enzyme on tumour and immune cells that converts AMP into adenosine, which switches off T and natural killer cells through A2A and A2B receptors. Oleclumab (anti-CD73) with durvalumab slowed progression in a phase 2 lung cancer trial and quemliclustat is in phase 3 in pancreatic cancer, but A2A blockers gave only modest signals and several were dropped.
CD39 converts extracellular ATP to AMP and CD73 (NT5E) converts AMP to adenosine, which suppresses T and NK cells via A2A/A2B receptors; hypoxia drives the axis. Oleclumab (anti-CD73) plus durvalumab improved PFS in the phase 2 COAST trial (stage III NSCLC) but the phase 3 PACIFIC-9 result is pending; quemliclustat (CD73 inhibitor) is in phase 3 in pancreatic cancer (PRISM-1); A2A antagonists (ciforadenant, etrumadenant, taminadenant) gave modest single-agent signals in RCC and prostate cancer and several were discontinued. CD39 antibodies (TTX-030) and uliledlimab continue in trials.
In plain words · CD73 is an enzyme on tumour and immune cells that converts AMP into adenosine, which switches off T and natural killer cells through A2A and A2B receptors. Oleclumab (anti-CD73) with durvalumab slowed progression in a phase 2 lung cancer trial and quemliclustat is in phase 3 in pancreatic cancer, but A2A blockers gave only modest signals and several were dropped.
CD73 is an enzyme on tumour and immune cells that converts AMP into adenosine, which switches off T and natural killer cells through A2A and A2B receptors. Oleclumab (anti-CD73) with durvalumab slowed progression in a phase 2 lung cancer trial and quemliclustat is in phase 3 in pancreatic cancer, but A2A blockers gave only modest signals and several were dropped.
Ecto-5'-nucleotidase anchored by GPI; produces adenosine that binds Gs-coupled A2A/A2B receptors, raising cAMP/PKA in lymphocytes and blunting TCR signalling, cytokine release and cytotoxicity; also promotes Treg and MDSC function.
2 products aim at CD73 / adenosine axis: antibodies. 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 NT5E: RNA tissue enhanced (cervix 106 nTPM); blood lineage group enriched (B-cells 33 nTPM, T-cells 31 nTPM); high antibody staining in 21 normal tissues; highest cancer staining colorectal cancer (10 of 12 high). Distribution: 5 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Pancreatic ductal adenocarcinoma, Lung cancer (all types), Breast cancer (all types), Renal cell carcinoma, Prostate cancer); 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 NT5E tissue; UniProt P21589; Open Targets ENSG00000135318 associations
First described 1990. Earliest sequence paper UniProt cites for the protein: Misumi et al, Eur. J. Biochem, 1990, "Primary structure of human placental 5'-nucleotidase and identification of the glycolipid anchor in the mature form". Source.
Ecto-5'-nucleotidase anchored by GPI; produces adenosine that binds Gs-coupled A2A/A2B receptors, raising cAMP/PKA in lymphocytes and blunting TCR signalling, cytokine release and cytotoxicity; also promotes Treg and MDSC function.
RNA: tissue enhanced (cervix 106 nTPM), detected in many normal tissues. Blood: group enriched (B-cells 33 nTPM, T-cells 31 nTPM).
Medium: Breast, Caudate, Cerebral cortex, Esophagus, Heart muscle, Kidney, Liver, Lymph node.
Medium only: testis cancer.
HPA NT5E tissue · HPA NT5E pathology · HPA protein class: CD markers
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.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Metastatic cancer | immune% | Immune-cell target (CD73 and adenosine on tumour and immune cells; tumour expression varies and is measured in trials): expressed on immune cells rather than on the tumour, so patient selection rests on the cancer type and, in trials, on PD-L1 or immune biomarkers. |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
AK119 is an experimental monoclonal antibody from Akeso in phase 2 trials for colorectal cancer, aimed at CD73 / adenosine axis.
Mavrostobart is an experimental monoclonal antibody from Phanes Therapeutics in phase 2 trials for non-small-cell lung cancer and pancreatic ductal adenocarcinoma, aimed at CD73 / adenosine axis.
Query for this target: (TITLE:"CD73 / adenosine axis" OR ABSTRACT:"CD73 / adenosine axis" OR TITLE:"NT5E" OR ABSTRACT:"NT5E") 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 CD73 / adenosine axis, not a curated reading list.
Shares A Phase I-II Study to Test the Safety and Efficacy of PD1 (AB122) and Adenosine Receptor (AB928) Antagonists With Chemotherapy After Short-Course Radiation for, Study of Quemliclustat and Chemotherapy Versus Placebo and Chemotherapy in Patients With Metastatic Pancreatic Ductal Adenocarcinoma, Quemliclustat, A Safety and Efficacy Study of Treatment Combinations With and Without Chemotherapy in Adult Participants With Advanced Upper Gastrointestinal Tract Malignancies.
Shares A Phase I-II Study to Test the Safety and Efficacy of PD1 (AB122) and Adenosine Receptor (AB928) Antagonists With Chemotherapy After Short-Course Radiation for, Study With Various Immunotherapy Treatments in Participants With Lung Cancer, A Safety and Efficacy Study of Treatment Combinations With and Without Chemotherapy in Adult Participants With Advanced Upper Gastrointestinal Tract Malignancies, Study of Novel Treatment Combinations in Patients With Lung Cancer.
Shares Study With Various Immunotherapy Treatments in Participants With Lung Cancer, A Safety and Efficacy Study of Treatment Combinations With and Without Chemotherapy in Adult Participants With Advanced Upper Gastrointestinal Tract Malignancies, Study of Novel Treatment Combinations in Patients With Lung Cancer, Gilead Sciences (incl. Kite).
Shares A Global Study to Assess the Effects of Durvalumab With Oleclumab or Durvalumab With Monalizumab Following Concurrent Chemoradiation in Patients With Stage III Unresectable Non-Small Cell Lung Cancer, The Selective Personalized Radio-Immunotherapy for Locally Advanced Non-Small Cell Lung Cancer Trial 2, Neoadjuvant and Adjuvant Treatment in Resectable Non-small Cell Lung Cancer, AstraZeneca.
Shares A Study to Compare Uliledlimab Combined With Toripalimab, Toripalimab Monotherapy, and Pembrolizumab Monotherapy in Patients With Previously Untreated Locally Advanced Unresectable or Metastatic PD-L1- and CD73- Selected Non-Small Cell Lung Cancer, A Study to Compare Uliledlimab Combined With Sintilimab and Chemotherapy Versus Sintilimab Combined With Chemotherapy in Patients With Previously Untr.
Shares Checkpoint (two meanings), PD-1 / PD-L1 immune checkpoint & T-cell activation, Pancreatic ductal adenocarcinoma, Prostate cancer.
Shares Mavrostobart, Dose Escalation/Expansion Study of Mavrostobart (PT199), an Anti-CD73 mAb, Administered Alone and in Combination With a PD-1 Inhibitor or Chemotherapy.
Shares A Study of GI-108, an Anti-CD73-IgG4 Fc-IL-2v Bispecific Fusion Protein, as Monotherapy in Patients With Advanced or Metastatic Solid Tumors, Renal cell carcinoma, Pancreatic ductal adenocarcinoma, Non-small-cell lung cancer.
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