Influence of syngeneic monoclonal anti-idiotypic antibodies to murine monoclonal antibodies against tumour-associated antigens on the biodistribution of their target antibodies and their fragments.

Abstract

The effect of syngeneic anti-idiotypic (anti-id) antibodies on the biodistribution of three murine monoclonal antibodies (mAb) against human tumour-associated antigens, and also on that of their fragments, has been examined in mice using, as a model system, purified anti-id mAb against three different target mAb. With the IgG2b mAb NCRC-2, pretreatment of mice 24 h previously with its IgG1 anti-id mAb NCRC-60 caused clearance of subsequently administered NCRC-2. With the univalent Fab/c fragment of NCRC-2 there was little effect, even with anti-id to Fab/c pretreatment ratios of 20:1, although immune complexes were present in the circulation. With Fab of NCRC-2, anti-id mAb prolonged blood survival by reducing renal clearance, immune complexes surviving in the circulation. With the IgG1 mAb NCRC-23, immune complexes formed in vivo with the IgG2b anti-id mAb NCRC-59, but with only little hepatic clearance. With the Fab and F(ab')2 fragments of NCRC-23, blood survival was increased in mice pretreated with anti-id mAb, and with Fab this was clearly due to reduced renal clearance. The third mAb, the IgG3 NCRC-48, formed complexes with its IgG2a anti-id mAb NCRC-62, but these survived in the circulation with no accelerated clearance of the target mAb. These results are different from those previously seen with endogenous anti-id responses. They indicate the diversity of effects that anti-id mAb can have on the biodistribution of their target mAb, and emphasise the difficulty of using such anti-id mAb to modulate the pharmacokinetics of target mAb.