The influence of syngeneic anti-idiotypic antibody on the biodistribution of an anti-tumour monoclonal antibody in BALB/c mice.

BALB/c mice were immunized against syngeneic murine 791T/36 monoclonal antibody (MAb) by intraperitoneal (i.p.) injection of the antibody conjugated to ricin toxin A chain. Subsequently, in these and control mice, the biodistribution of radioiodinated 791T/36 antibody and isotype-matched (IgG2b) control immunoglobulin was examined. Pre-treated mice showed marked perturbation of biodistribution of the 791T/36 antibody but not of control IgG2b. This was manifest as rapid hepatic clearance of the antibody which was followed by accelerated catabolism and excretion of the radiolabel. Anti-idiotypic antibodies were identified in immunotoxin pretreated mice by their ability to inhibit the binding of FITC-labelled 791T/36 antibody to tumour target cells. These studies show that antibody responses, even to only the idiotype of a MAb, may produce marked perturbation of its biodistribution. This has implications for the clinical use of human or chimeric MAbs for tumour imaging or targeting of therapeutic agents since, if anti-idiotypic antibodies are evoked, they could still prevent tumour localization of antibody or conjugate.