Influence of syngeneic (anti-idiotypic) antibody responses on biodistribution and tumour localisation of murine monoclonal antibodies and fragments.
Balb/c mice were immunised with three different syngeneic monoclonal antibodies (Mabs). Following injection of radiolabelled Mabs into mice with anti-antibody responses they were cleared from the circulation, predominantly to the liver, due to the formation of immune complexes. Anti-antibody titres as low as 1/100 were virtually as effective as 1/3,000 in perturbing biodistribution of Mabs. There were no effects against isotype matched control Mabs. There was a much lesser effect against Fab or F (ab')2 of one Mab, although these did form immune complexes in the circulation of immune mice. With Fab of another Mab its blood survival was actually prolonged, due to immune complex formation. With this Fab, although blood survival was prolonged, localisation into human tumour xenografts expressing its target antigen in Nude mice was reduced by pre-treatment with immune serum. These studies show that syngeneic (anti-idiotypic) responses have a detrimental effect on the pharmacokinetics of Mabs, but with more diverse effects on their fragments. With fragments the indication is that even when biodistribution is not grossly perturbed, tumour recognition may still be restricted.
Pimm
M V
MV
Cancer Research Campaign Laboratory, University of Nottingham, Great Britain.
Gribben
S J
SJ
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis / Q000502:physiology*; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D000917:Antibody Formation; D006801:Humans; D007114:Immunization; D007128:Immunoglobulin Fragments / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000097:blood / Q000276:immunology* / Q000378:metabolism*; D012516:Osteosarcoma / Q000097:blood / Q000276:immunology / Q000378:metabolism; D013274:Stomach Neoplasms / Q000097:blood / Q000276:immunology / Q000378:metabolism; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007128:Immunoglobulin Fragments