Pharmacokinetics and microdistribution of polyethylene glycol‐modified humanized A33 antibody targeting colon cancer xenografts

Therapeutic proteins have been conjugated with polyethylene glycol (PEGylation) to reduce immunogenicity and enhance circulating dose. Here we have investigated the effect of PEGylation on immunogenicity, pharmacokinetics, and histologic microdistribution of tumor‐targeting antibodies with humanized...

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Bibliographic Details
Published in:International journal of cancer 2000-08, Vol.87 (3), p.382-390
Main Authors: Deckert, P. Markus, Jungbluth, Achim, Montalto, Nicholas, Clark, Mike A., Finn, Ronald D., Williams Jr, Clarence, Richards, Elizabeth C., Panageas, Katherine S., Old, Lloyd J., Welt, Sydney
Format: Article
Language:English
Subjects:
Adenocarcinoma - immunology
Animals
Antibodies, Monoclonal - analysis
Antibodies, Monoclonal - immunology
Antibodies, Monoclonal - pharmacokinetics
Antigens, Neoplasm - immunology
Biological and medical sciences
Colonic Neoplasms - immunology
Female
Half-Life
Humans
Immunization
Immunoenzyme Techniques
Immunoglobulin G - analysis
Immunoglobulin G - immunology
Iodine Radioisotopes - analysis
Iodine Radioisotopes - pharmacokinetics
Medical sciences
Membrane Glycoproteins - immunology
Mice
Mice, Nude
Molecular Weight
Neoplasm Transplantation
Polyethylene Glycols - analysis
Polyethylene Glycols - pharmacokinetics
Radiation therapy and radiosensitizing agent
Radioimmunodetection
Tissue Distribution
Transplantation, Heterologous
Treatment with physical agents
Treatment. General aspects
Tumors
Citations: Items that this one cites
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Summary:Therapeutic proteins have been conjugated with polyethylene glycol (PEGylation) to reduce immunogenicity and enhance circulating dose. Here we have investigated the effect of PEGylation on immunogenicity, pharmacokinetics, and histologic microdistribution of tumor‐targeting antibodies with humanized A33 antibody (huA33) as a model system. Conjugation of huA33 with methoxy‐PEG of Mr 5,000 (32%–34% of primary amines modified) or Mr 20,000 (16%–18% modification) preserved >50% of native huA33 binding to SW1222 colon cancer cells. In mice, both PEGylated forms cleared from serum moderately slower than native huA33. After repeated immunization with PEG‐huA33, antiantibody titers in immunocompetent mice were
ISSN:0020-7136
1097-0215
DOI:10.1002/1097-0215(20000801)87:3<382::AID-IJC12>3.0.CO;2-P