INFLUENCE OF SYNGENEIC (ANTIIDIOTYPIC) ANTIBODY-RESPONSES ON BIODISTRIBUTION AND TUMOR-LOCALIZATION OF MURINE MONOCLONAL-ANTIBODIES AND FRAGMENTS

Balb/c mice were immunised with three different syngeneic monoclonal a ntibodies (Mabs). Following injection of radiolabelled Mabs into mice with anti-antibody responses they were cleared from the circulation, p redominantly to the fiver, due to the formation of immune complexes. A nti-antibody titres as low as 1/100 were virtually as effective as 1/3 ,000 in perturbing biodistribution of Mabs. There were no effects agai nst isotype matched control Mabs. There was a much lesser effect again st Fab or F (ab')2 of one Mab, although these did form immune complexe s in the circulation of immune mice. With Fab of another Mab its blood survival was actually prolonged, due to immune complex formation. Wit h this Fab, although blood survival was prolonged, localisation into h uman tumour xenografts expressing its target antigen in Nude mice was reduced by pre-treatment with immune serum. These studies show that sy ngeneic (anti-idiotypic) responses have a detrimental effect on the ph armacokinetics of Mabs, but with more diverse effects on their fragmen ts. With fragments the indication is that even when biodistribution is not grossly perturbed, tumour recognition may still be restricted.