ArticleJournal for immunotherapy of cancer2022
Targeting two distinct epitopes on human CD73 with a bispecific antibody improves anticancer activity.
Article in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- 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
- The CD73-adenosine axis in melanoma: from multidimensional regulation to precision immunotherapy.Frontiers in immunology · 2026Review
- Purinergic pathways and their clinical use in the treatment of acute myeloid leukemia.Purinergic signalling · 2025Review
- Research progress of CD73-adenosine signaling regulating hepatocellular carcinoma through tumor microenvironment.Journal of experimental & clinical cancer research : CR · 2025Review
- Immune cell metabolic reprogramming in hepatocellular carcinoma: mechanisms, tumor microenvironment, and future immunotherapeutic directions.Frontiers in immunology · 2025Review
- An antibody cocktail targeting two different CD73 epitopes enhances enzyme inhibition and tumor control.Nature communications · 2024Article
- Adenosine and Its Receptors in the Pathogenesis and Treatment of Inflammatory Skin Diseases.International journal of molecular sciences · 2024Review
- The present and future of bispecific antibodies for cancer therapy.Nature reviews. Drug discovery · 2024Review
- Adoptive cell transfer therapy with ex vivo primed peripheral lymphocytes in combination with anti-PDL1 therapy effectively inhibits triple-negative breast cancer growth and metastasis.Molecular cancer · 2024Article
- Current perspectives and trends of CD39-CD73-eAdo/A2aR research in tumor microenvironment: a bibliometric analysis.Frontiers in immunology · 2024Article
- Review
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundImmunosuppressive extracellular adenosine is generated by the enzymatic activity of CD73. In preclinical models, antibodies (Abs) targeting different epitopes on CD73 exert anticancer activity through distinct mechanisms such as inhibition of enzymatic activity, engagement of Fc receptors, and spatial redistribution of CD73.
methodsUsing controlled Fab arm exchange, we generated biparatopic bispecific antibodies (bsAbs) from parental anti-CD73 Abs with distinct anticancer activities. The resulting anticancer activity was evaluated using in vitro and in vivo models.
resultsWe demonstrate that different anticancer activities can be combined in a biparatopic bsAb. Remarkably, the bsAb significantly improved the enzyme inhibitory activity compared with the parental Abs, which led to neutralization of adenosine-mediated T-cell suppression as demonstrated by proliferation and interferon gamma (IFN-γ) production and prolonged survival of tumor-bearing mice. Additionally, the bsAb caused more efficient internalization of cell surface CD73 and stimulated potent Fc-mediated engagement of human immune effector cells in vitro and in vivo.
conclusionsOur data collectively demonstrate that complementary anticancer mechanisms of action of distinct anti-CD73 Abs can be combined and enhanced in a biparatopic bsAb. The multiple mechanisms of action and superior activity compared with the monospecific parental Abs make the bsAb a promising candidate for therapeutic targeting of CD73 in cancer. This concept may greatly improve future Ab design.
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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.