ArticleMolecular oncology2016
Dual Constant Domain-Fab: A novel strategy to improve half-life and potency of a Met therapeutic antibody.
Article in Molecular oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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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.
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Who cites it
9 citing papers in PubMed, 14 citations in OpenAlex.
- Anti-cancer therapeutic strategies based on HGF/MET, EpCAM, and tumor-stromal cross talk.Cancer cell international · 2022Review
- hOA-DN30: a highly effective humanized single-arm MET antibody inducing remission of 'MET-addicted' cancers.Journal of experimental & clinical cancer research : CR · 2022Article
- Mechanistic principles of an ultra-long bovine CDR reveal strategies for antibody design.Nature communications · 2021Article
- Proteolytic cleavages of MET: the divide-and-conquer strategy of a receptor tyrosine kinase.BMB reports · 2019Review
- Met inhibition revokes IFNγ-induction of PD-1 ligands in MET-amplified tumours.British journal of cancer · 2019Article
- Overexpression-mediated activation of MET in the Golgi promotes HER3/ERBB3 phosphorylation.Oncogene · 2019Article
- Review
- Site-specific PEGylation of an anti-CEA/CD3 bispecific antibody improves its antitumor efficacy.International journal of nanomedicine · 2018Article
- Dual Constant Domain-Fab: A novel strategy to improve half-life and potency of a Met therapeutic antibody.Molecular oncology · 2016Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The kinase receptor encoded by the Met oncogene is a sensible target for cancer therapy. The chimeric monovalent Fab fragment of the DN30 monoclonal antibody (MvDN30) has an odd mechanism of action, based on cell surface removal of Met via activation of specific plasma membrane proteases. However, the short half-life of the Fab, due to its low molecular weight, is a severe limitation for the deployment in therapy. This issue was addressed by increasing the Fab molecular weight above the glomerular filtration threshold through the duplication of the constant domains, in tandem (DCD-1) or reciprocally swapped (DCD-2). The two newly engineered molecules showed biochemical properties comparable to the original MvDN30 in vitro, acting as full Met antagonists, impairing Met phosphorylation and activation of downstream signaling pathways. As a consequence, Met-mediated biological responses were inhibited, including anchorage-dependent and -independent cell growth. In vivo DCD-1 and DCD-2 showed a pharmacokinetic profile significantly improved over the original MvDN30, doubling the circulating half-life and reducing the clearance. In pre-clinical models of cancer, generated by injection of tumor cells or implant of patient-derived samples, systemic administration of the engineered molecules inhibited the growth of Met-addicted tumors.
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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.