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

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Abstract
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 pre‐treated 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.