ArticleProceedings of the National Academy of Sciences of the United States of America2015
Functional human antibody CDR fusions as long-acting therapeutic endocrine agonists.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 32 citations in OpenAlex.
- Stability convergence in natural antibodies with ultra-long hypervariable loops.Communications biology · 2025Article
- Rational design of humanized antibody inhibitors for cathepsin S.Archives of biochemistry and biophysics · 2024Article
- Article
- Antibody Libraries as Tools to Discover Functional Antibodies and Receptor Pleiotropism.International journal of molecular sciences · 2021Review
- Strategies for targeting cell surface proteins using multivalent conjugates and chemical biology.Methods in cell biology · 2021Article
- Long-acting antibody ligand mimetics for HER4-selective agonism.Scientific reports · 2020Article
- Selection of a Full Agonist Combinatorial Antibody that Rescues Leptin Deficiency In Vivo.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020Article
- Rational Design of a Humanized Antibody Inhibitor of Cathepsin B.Biochemistry · 2020Article
- Article
- Rational Design of Dual Agonist-Antibody Fusions as Long-acting Therapeutic Hormones.ACS chemical biology · 2016Article
- Rational design of a Kv1.3 channel-blocking antibody as a selective immunosuppressant.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Stabilizing the CH2 Domain of an Antibody by Engineering in an Enhanced Aromatic Sequon.ACS chemical biology · 2016Article
- Conservation and diversity in the ultralong third heavy-chain complementarity-determining region of bovine antibodies.Science immunology · 2016Article
- Distinct antibody species: structural differences creating therapeutic opportunities.Current opinion in immunology · 2016Review
- Non-covalent carriage of anticancer agents by humanized antibody trastuzumab.Journal of molecular modeling · 2016Article
- Engineering a long-acting, potent GLP-1 analog for microstructure-based transdermal delivery.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Switch-mediated activation and retargeting of CAR-T cells for B-cell malignancies.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- An Epitope-Specific Respiratory Syncytial Virus Vaccine Based on an Antibody Scaffold.Angewandte Chemie (International ed. in English) · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
On the basis of the 3D structure of a bovine antibody with a well-folded, ultralong complementarity-determining region (CDR), we have developed a versatile approach for generating human or humanized antibody agonists with excellent pharmacological properties. Using human growth hormone (hGH) and human leptin (hLeptin) as model proteins, we have demonstrated that functional human antibody CDR fusions can be efficiently engineered by grafting the native hormones into different CDRs of the humanized antibody Herceptin. The resulting Herceptin CDR fusion proteins were expressed in good yields in mammalian cells and retain comparable in vitro biological activity to the native hormones. Pharmacological studies in rodents indicated a 20- to 100-fold increase in plasma circulating half-life for these antibody agonists and significantly extended in vivo activities in the GH-deficient rat model and leptin-deficient obese mouse model for the hGH and hLeptin antibody fusions, respectively. These results illustrate the utility of antibody CDR fusions as a general and versatile strategy for generating long-acting protein therapeutics.
Indexed as
Identifiers
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.