Pegylated CytokinesPotential Application in Immunotherapy of Cancer
作者:
James F. Eliason,
期刊:
BioDrugs
(ADIS Available online 2001)
卷期:
Volume 15,
issue 11
页码: 705-711
ISSN:1173-8804
年代: 2001
出版商: ADIS
关键词: Antineoplastics, pharmacodynamics;Cancer;Immunomodulators, pharmacodynamics;PEG filgrastim, pharmacodynamics;PEG interferon alpha 2a, pharmacodynamics;PEG TNF, pharmacodynamics;Pegacaristim, pharmacodynamics;Pegaldesleukin, pharmacodynamics;Research and d
数据来源: ADIS
摘要:
Conjugation of the polymer polyethylene glycol (PEG) to proteins can significantly decrease their clearance from plasma, thus increasing their half-livesin vivo. The increased half-life of PEG-proteins is directly proportional to the total molecular weight of the construct. This approach has been used to design cytokine constructs that can be administered once a week, rather than on a daily or alternate-day schedule. Two cytokines for which this approach appears to be successful are PEG−interferon-α-2a (PEG−IFNα-2a) and PEG-granulocyte colony- stimulating factor (PEG−G-CSF). Both use high molecular weight PEG (20 to 40kD) to give sufficiently long durationin vivo. In the case of PEG−G-CSF conjugates, thein vivoefficacy is directly proportional to molecular weight, whereas thein vitroactivity is inversely proportional, suggesting that overall duration of contact is more important than the affinity of the interaction. Conjugates of a number of other cytokines have been prepared, but until recently, few have used the high molecular weight polymers. In the future, as this approach is taken to make new PEG-cytokine constructs, thorough pharmacokinetic studies will be essential for their development and clinical use.
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