A chemically defined trifunctional antibody-cytokine-drug conjugate with potent antitumor activity

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A chemically defined trifunctional antibody-cytokine-drug conjugate with potent antitumor activity

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Publication Article, peer reviewed scientific
Title A chemically defined trifunctional antibody-cytokine-drug conjugate with potent antitumor activity
Author(s) List, Thomas ; Casi, Giulio ; Neri, Dario
Date 2014
English abstract
The combination of immunostimulatory agents with cytotoxic drugs is emerging as a promising approach for potentially curative tumor therapy, but advances in this field are hindered by the requirement of testing individual combination partners as single agents in dedicated clinical studies, often with suboptimal efficacy. Here, we describe for the first time a novel multipayload class of targeted drugs, the immunocytokine-drug conjugates (IDC), which combine a tumor-homing antibody, a cytotoxic drug, and a proinflammatory cytokine in the same molecular entity. In particular, the IL2 cytokine and the disulfide-linked maytansinoid DM1 microtubular inhibitor could be coupled to the F8 antibody, directed against the alternatively spliced EDA domain of fibronectin, in a site-specific manner, yielding a chemically defined product with selective tumor-homing performance and potent anticancer activity in vivo, as tested in two different immunocompetent mouse models.
DOI http://dx.doi.org/10.1158/1535-7163.MCT-14-0599 (link to publisher's fulltext)
Publisher American Association for Cancer Research
Host/Issue Molecular cancer therapeutics;11
Volume 13
ISSN 1535-7163
Pages 2641-2652
Language eng (iso)
Subject(s) Medicine
Research Subject Categories::ODONTOLOGY
Handle http://hdl.handle.net/2043/17976 (link to this page)

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