PMID: 7515280Jan 1, 1994Paper

In vivo activities of acidic fibroblast growth factor-Pseudomonas exotoxin fusion proteins

Bioconjugate Chemistry
C B SiegallI Pastan

Abstract

Fibroblast growth factor receptors are highly expressed in a variety of cancer cells and activated vasculature. Using chimeric toxins targeted to cell-surface a FGF receptors, we have demonstrated specific cytotoxic activity to these cell types. These molecules, aFGF-PE40 and aFGF-PE40 KDEL, are fusion proteins containing acidic FGF and either a 40- or a 66-kDa binding defective form of Pseudomonas exotoxin, respectively. Both aFGF-toxin fusion proteins were able to inhibit protein synthesis in vitro in a variety of carcinoma cell lines. The half-life of aFGF-PE40 in serum was found to be 41 min when coadministered with heparin. Administration of aFGF-PE40 or aFGF-PE4E KDEL with heparin inhibits the growth of established KB and preestablished A431 epidermoid carcinoma xenografts in athymic mice. The antitumor activities of the two aFGF-toxin fusion proteins were equivalent against the KB tumor xenografts. While we were able to slow the growth of the KB tumor xenografts, we were unable to cause tumor regressions. Histochemical analysis of treated versus untreated tumor tissue revealed a difference in tumor size but not of vascularity. We conclude that aFGF-PE40 and aFGF-PE4E KDEL have in vivo antitumor activity that targets the ...Continue Reading

Citations

Jun 6, 2000·Advanced Drug Delivery Reviews·I Pastan, R J Kreitman
Dec 12, 2012·International Journal of Nanomedicine·Anna SzlachcicJacek Otlewski
Oct 16, 2004·Molecular and Cellular Neurosciences·Gunnar P H Dietz, Mathias Bähr
Nov 4, 2000·Expert Opinion on Investigational Drugs·L A Kueltzo, C R Middaugh
Jul 5, 2005·Expert Opinion on Investigational Drugs·R J Kreitman
Sep 2, 2003·Journal of Pharmaceutical Sciences·Lisa A Kueltzo, C Russell Middaugh
Sep 12, 2002·Expert Opinion on Therapeutic Targets·Michael JeffersHenri S Lichenstein
Aug 1, 1994·Cancer·C B Siegall
Dec 17, 1997·International Journal of Cancer. Journal International Du Cancer·T A OlsonS Ramakrishnan
Jul 17, 2021·Frontiers in Pharmacology·Sven SeiwerthPredrag Sikiric
Dec 8, 2009·Bioorganic & Medicinal Chemistry Letters·Thommey P ThomasJames R Baker

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