ArticleProceedings of the National Academy of Sciences of the United States of America2007
Synthesis of the next-generation therapeutic antibodies that combine cell targeting and antibody-catalyzed prodrug activation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. 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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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
12 citing papers in PubMed.
- Review
- A new immunochemical strategy for triple-negative breast cancer therapy.Scientific reports · 2021Article
- Glycoconjugation: An approach to cancer therapeutics.World journal of clinical oncology · 2020Review
- Convenient Method of Synthesizing Aryloxyalkyl Esters from Phenolic Esters Using Halogenated Alcohols.Molecules (Basel, Switzerland) · 2018Article
- Characterization of a fusion protein of RGD4C and the β-lactamase variant for antibody-directed enzyme prodrug therapy.OncoTargets and therapy · 2014Article
- Versatile approach to α-alkoxy carbamate synthesis and stimulus-responsive alcohol release.Organic & biomolecular chemistry · 2012Article
- Comparison of designed and randomly generated catalysts for simple chemical reactions.Protein science : a publication of the Protein Society · 2012Article
- Structure-activity relationship study of collagen-derived anti-angiogenic biomimetic peptides.Chemical biology & drug design · 2012Article
- Targeting cell surface alpha(v)beta(3) integrin increases therapeutic efficacies of a legumain protease-activated auristatin prodrug.Molecular pharmaceutics · 2012Article
- The legumain protease-activated auristatin prodrugs suppress tumor growth and metastasis without toxicity.ChemMedChem · 2011Article
- Targeted delivery of paclitaxel to tumor cells: synthesis and in vitro evaluation.Journal of medicinal chemistry · 2010Article
- Studies toward the duocarmycin prodrugs for the antibody prodrug therapy approach.Tetrahedron letters · 2009Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
An obstacle in the utilization of catalytic Abs for selective prodrug activation in cancer therapy has been systemic tumor targeting. Here we report the generation of catalytic Abs that effectively target tumor cells with undiminished prodrug activation capability. Ab conjugates were prepared by covalent conjugation of an integrin alpha(v)beta(3)-targeting antagonist to catalytic Ab 38C2 through either sulfide groups of cysteine residues generated by reduction of the disulfide bridges in the hinge region or surface lysine residues not involved in the catalytic activity. Using flow cytometry, the Ab conjugates were shown to bind efficiently to integrin alpha(v)beta(3)-expressing human breast cancer cells. The Ab conjugates also retained the retro-aldol activity of their parental catalytic Ab 38C2, as measured by methodol and doxorubicin (dox) prodrug activation. Complementing these Ab conjugates, an evolved set of dox prodrugs was designed and synthesized. Dox prodrugs that showed higher stability and lower toxicity were evaluated both in the presence and absence of the integrin alpha(v)beta(3)-targeting 38C2 conjugates for cell-killing efficacy by using human breast cancer cells. Our study reveals that cell targeting and prodrug activation capabilities can be efficiently combined for selective chemotherapy with novel dox prodrugs.
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