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Int. J. Mol. Sci. 2015, 16(5), 9625-9634; doi:10.3390/ijms16059625

A Fusion Protein of RGD4C and β-Lactamase Has a Favorable Targeting Effect in Its Use in Antibody Directed Enzyme Prodrug Therapy

Tianjin Key Lab of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China
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Academic Editor: Katalin Prokai-Tatrai
Received: 11 February 2015 / Revised: 20 April 2015 / Accepted: 22 April 2015 / Published: 28 April 2015
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
View Full-Text   |   Download PDF [990 KB, uploaded 28 April 2015]   |  

Abstract

Antibody directed enzyme prodrug therapy (ADEPT) utilizing β-lactamase is a promising treatment strategy to enhance the therapeutic effect and safety of cytotoxic agents. In this method, a conjugate (antibody-β-lactamase fusion protein) is employed to precisely activate nontoxic cephalosporin prodrugs at the tumor site. A major obstacle to the clinical translation of this method, however, is the low catalytic activity and high immunogenicity of the wild-type enzymes. To overcome this challenge, we fused a cyclic decapeptide (RGD4C) targeting to the integrin with a β-lactamase variant with reduced immunogenicity which retains acceptable catalytic activity for prodrug hydrolysis. Here, we made a further investigation on its targeting effect and pharmacokinetic properties, the results demonstrated that the fusion protein retains a targeting effect on integrin positive cells and has acceptable pharmacokinetic characteristics, which benefits its use in ADEPT. View Full-Text
Keywords: antibody directed enzyme prodrug therapy; RGD4C; β-lactamase; targeting antibody directed enzyme prodrug therapy; RGD4C; β-lactamase; targeting
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Wang, H.; Zhou, X.-L.; Long, W.; Liu, J.-J.; Fan, F.-Y. A Fusion Protein of RGD4C and β-Lactamase Has a Favorable Targeting Effect in Its Use in Antibody Directed Enzyme Prodrug Therapy. Int. J. Mol. Sci. 2015, 16, 9625-9634.

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