PEGylation confers greatly extended half-life and attenuated immunogenicity to recombinant methioninase in primates

Cancer Research
Zhijian YangR M Hoffman

Abstract

Methionine depletion by recombinant methioninase (rMETase) has been demonstrated previously to be highly effective in tumor-bearing mouse models. However, the therapeutic potential of rMETase has been limited by its short plasma half-life and immunologic effects, including high antibody production in mice and monkeys and anaphylactic reactions in monkeys. To overcome these limits of rMETase, the enzyme has been coupled to methoxypolyethylene glycol succinimidyl glutarate (MEGC-PEG-5000). In this study, we evaluated the pharmacokinetics, antigenicity and toxicity of MEGC-PEG-rMETase in Macaca fascicularis monkeys using an escalating-dose strategy. Dose ranging studies at 1,000, 4,000, and 8,000 units/kg i.v. determined that a single dose of 4,000 units/kg was sufficient to reduce plasma methionine to <5 micromol/L for 12 hours. Pharmacokinetic analysis with the single 4,000 units/kg dose showed that MEGC-PEG-rMETase holoenzyme activity was eliminated with a biological half-life of 1.3 hours, and the MEGC-PEG-rMETase apoenzyme was eliminated with a biological half-life of 90 hours, an approximately 36-fold increase compared with non-PEGylated rMETase. A single dose at 2,000 units/kg of MEGC-PEG-rMETase resulted in an apoenzyme ha...Continue Reading

References

May 1, 1976·Proceedings of the National Academy of Sciences of the United States of America·R M Hoffman, R W Erbe
Apr 20, 1990·Science·R Pool
Jan 1, 1987·Methods in Enzymology·N Esaki, K Soda
Dec 16, 1983·Biochemical and Biophysical Research Communications·J O MechamR M Hoffman
Sep 1, 1995·Clinical Immunology and Immunopathology·M S Hershfield
Jun 8, 2001·Journal of Controlled Release : Official Journal of the Controlled Release Society·A Kozlowski, J M Harris
Mar 26, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Zhijian YangRobert M Hoffman

❮ Previous
Next ❯

Citations

Nov 21, 2008·Journal of the American Society for Mass Spectrometry·Chul YooMinhui Ma
Aug 11, 2006·Nature Reviews. Cancer·Ruth Duncan
Jul 7, 2011·International Journal of Molecular Sciences·Zhendong LiuHan-Mei Xu
Dec 17, 2011·Expert Opinion on Biological Therapy·Vaidehi AgrawalArthur E Frankel
Dec 13, 2012·Expert Opinion on Drug Discovery·Pascal Richette, Ricardo Garay
Aug 31, 2012·Expert Opinion on Drug Delivery·Ricardo P GarayPascal Richette
Aug 14, 2012·Enzyme and Microbial Technology·Ashraf S El-SayedHatem M Nassrat
Aug 13, 2009·Advanced Drug Delivery Reviews·Gianfranco Pasut, Francesco M Veronese
Jun 17, 2014·Bioconjugate Chemistry·Sheng DingVolker Schellenberger
Sep 22, 2007·Advanced Drug Delivery Reviews·David Filpula, Hong Zhao
Sep 18, 2007·Advanced Drug Delivery Reviews·Gianfranco PasutFrancesco M Veronese
Jan 18, 2006·Biochemical Pharmacology·Valerie PavillardRoger M Phillips
Jul 15, 2015·The British Journal of Radiology·C von NeubeckM Krause
Jun 6, 2013·Journal of Controlled Release : Official Journal of the Controlled Release Society·Sung In LimInchan Kwon
May 15, 2013·Journal of Controlled Release : Official Journal of the Controlled Release Society·Ibrahim YildizNicole F Steinmetz
May 10, 2011·Toxicon : Official Journal of the International Society on Toxinology·Fernando FratelliCelso Pereira Caricati
Apr 28, 2016·Expert Opinion on Drug Delivery·Anisha A D'souza, Ranjita Shegokar
Oct 29, 2015·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Amy M WenNicole F Steinmetz
Jul 31, 2018·Expert Opinion on Drug Metabolism & Toxicology·Shenglei YanJingqing Zhang
Jun 19, 2019·Bioanalysis·Sophie Tourdot, Timothy P Hickling
Aug 10, 2016·Advanced Materials·Vahid RaeesiWarren C W Chan
Oct 26, 2013·Nanotechnology·Michael A BruckmanNicole F Steinmetz
Sep 10, 2009·Bioconjugate Chemistry·Chien-Hsing ChangDavid M Goldenberg
Jun 8, 2021·Frontiers in Endocrinology·Ryan A LaffertyPeter R Flatt
Jan 14, 2019·ACS Biomaterials Science & Engineering·Chetan NehateVeena Koul
Sep 20, 2021·Drug Discovery Today·Jennifer N Hennigan, Michael D Lynch

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anaphylaxis

Anaphylaxis is a serious allergic reaction that is rapid in onset and may cause death.