ArticleJournal of controlled release : official journal of the Controlled Release Society2012
Site-specific targeting of antibody activity in vivo mediated by disease-associated proteases.
Article in Journal of controlled release : official journal of the Controlled Release Society, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 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
38 citing papers in PubMed, 65 citations in OpenAlex.
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Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
As a general strategy to selectively target antibody activity in vivo, a molecular architecture was designed to render binding activity dependent upon proteases in disease tissues. A protease-activated antibody (pro-antibody) targeting vascular cell adhesion molecule 1 (VCAM-1), a marker of atherosclerotic plaques, was constructed by tethering a binding site-masking peptide to the antibody via a matrix metalloprotease (MMP) susceptible linker. Pro-antibody activation in vitro by MMP-1 yielded a 200-fold increase in binding affinity and restored anti-VCAM-1 binding in tissue sections from ApoE⁻/⁻ mice ex vivo. The pro-antibody was efficiently activated by native proteases in aorta tissue extracts from ApoE⁻/⁻, but not from normal mice, and accumulated in aortic plaques in vivo with enhanced selectivity when compared to the unmodified antibody. Pro-antibody accumulation in aortic plaques was MMP-dependent, and significantly inhibited by a broad-spectrum MMP inhibitor. These results demonstrate that the activity of disease-associated proteases can be exploited to site-specifically target antibody activity in vivo.
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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.