Coupling of the antitumoral enzyme bovine seminal ribonuclease to polyethylene glycol chains increases its systemic efficacy in mice

Anti-cancer Drugs
M MichaelisJ Matousek

Abstract

Bovine seminal ribonuclease (BS-RNase) is an antitumoral active enzyme exhibiting specific antitumoral action against a number of different cancer cell lines. However, its systemic use is limited by its pharmacokinetic properties and antigenicity. Therefore, it was conjugated to polyethylene glycol (PEG) chains to overcome these problems. Measurement of aspermatogenic effects of the preparation after s.c. injection and injection into the scrotum was chosen as a model for the distribution of the enzyme in the body mediated by the linkage to PEG chains. Additionally, the antigenicity of BS-RNase coupled to PEG chains (BS-RNase-PEG) was compared to that of free BS-RNase, as antigenicity is known to be one of the main obstacles in the use of protein-based drugs. BS-RNase-PEG caused aspermatogenic effects after systemic administration to mice in very low concentrations at which free BS-RNase is not effective. Moreover, BS-RNase possessed a very low antigenicity as long as it was coupled to the PEG chains. In order to investigate the antitumoral efficacy of BS-RNase-PEG in vivo, preliminary experiments on the effect of the conjugate on neuroblastoma growth in mice were performed in a UKF-NB-3 xeno-transplantate model, demonstrating a...Continue Reading

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Citations

Mar 12, 2004·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Josef MatousekRonald T Raines
Jan 28, 2004·Journal of Controlled Release : Official Journal of the Controlled Release Society·Josef MatousekJirí Skvor
Aug 3, 2013·Translational Oncology·Thomas J RutkoskiRonald T Raines
Nov 25, 2014·Langmuir : the ACS Journal of Surfaces and Colloids·Yang WeiRobert A Latour
Apr 21, 2005·Biotechnology and Bioengineering·Susan M DalyRobert D Tilton
Nov 12, 2010·Langmuir : the ACS Journal of Surfaces and Colloids·Sheetal S PaiRobert D Tilton
Feb 9, 2005·Langmuir : the ACS Journal of Surfaces and Colloids·Susan M DalyRobert D Tilton

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