Polyethylene glycol modification of a galactosylated streptavidin clearing agent: effects on immunogenicity and clearance of a biotinylated anti-tumour antibody.
Effective radioimmunotherapy is limited by slow antibody clearance from the circulation, which results in low tumour to blood ratios and restricts the dose of radiolabelled anti-tumour antibody that can be safely administrated. Avidin and streptavidin clearing agents have been shown to effectively complex and clear radioactive biotinylated antibodies from the circulation, but their immunogenicity may limit their repeated use. We have investigated whether polyethylene glycol (PEG) modification can reduce the immunogenicity of our galactosylated streptavidin (gal-streptavidin) clearing agent without altering its effectiveness as a clearing agent. The immune response evoked in mice after intraperitoneal infection of 30 micrograms of gal-streptavidin was decreased after PEG modification, as shown by lower antibody titres and a reduction in the number of mice that elicited an anti-gal-streptavidin response. The effect of PEG-modified gal-streptavidin on the blood clearance and tumour localisation of a 125I-labelled biotinylated anti-CEA was investigated in the LS174T human colon carcinoma xenograft in nude mice. Although PEG modified gal-streptavidin bound the [125I]biotinylated antibody in vivo, effective clearance from the circulation was inhibited, resulting in very little reduction in the levels of circulation radioactivity, together with a decrease in the antibody localised to the tumour.
Marshall
D
D
Cancer Research Campaign Laboratories, Department of Clinical Oncology, Royal Free Hospital School of Medicine, London, UK.
Pedley
R B
RB
Boden
J A
JA
Boden
R
R
Melton
R G
RG
Begent
R H
RH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism* / Q000493:pharmacokinetics; D000912:Antibodies, Neoplasm / Q000378:metabolism*; D001426:Bacterial Proteins / Q000276:immunology / Q000494:pharmacology*; D001710:Biotin; D002850:Chromatography, Gel; D006801:Humans; D008657:Metabolic Clearance Rate; D051379:Mice; D008970:Molecular Weight; D011092:Polyethylene Glycols / Q000494:pharmacology*; D016499:Radioimmunotherapy; D019809:Streptavidin
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D001426:Bacterial Proteins; D011092:Polyethylene Glycols; D001710:Biotin; D019809:Streptavidin