The influence of anti-(ricin toxin A chain) monoclonal antibodies on the pharmacokinetics of ricin toxin A chain and recombinant ricin A chain in mice.
Two monoclonal antibodies against ricin toxin A chain (RTA) have been examined for their effects on the blood survival and biodistribution of RTA and recombinant ricin A chain in mice. When admixed with the toxins at 1:1 molar ratios prior to intravenous injection, the antibodies prolonged blood survival and whole-body retention of both species of RTA, and this was due essentially to reduced renal clearance of the toxins. Immune complexes were identified by gel filtration chromatography and immune precipitation with anti-IgG antiserum in mixtures prior to injection and in the serum of mice injected with the mixtures. An irrelevant monoclonal antibody showed no complex formation, and no effect on biodistribution. These studies have shown that immune complexes formed between monoclonal antibodies and protein antigens of molecular mass up to at least 30 kDa survive in the circulation, rather than being cleared by the reticuloendothelial system. Such antibodies could be used to modulate the biodistribution of toxic molecules such as ribosome-inhibiting proteins like RTA. This might be exploited therapeutically, for example in the construction of bispecific antibodies against ribosomal inhibiting proteins and tumour-associated antigens.
Pimm
M V
MV
Cancer Research Campaign Laboratories, University of Nottingham, UK.
Gunn
B
B
Lord
J M
JM
Baldwin
R W
RW
D000818:Animals; D000936:Antigen-Antibody Complex; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008657:Metabolic Clearance Rate; D051379:Mice; D011994:Recombinant Proteins / Q000493:pharmacokinetics*; D012276:Ricin / Q000276:immunology / Q000493:pharmacokinetics*; D013997:Time Factors; D014018:Tissue Distribution
D000936:Antigen-Antibody Complex; D011994:Recombinant Proteins; D012276:Ricin