Influence of circulating antigen on the biodistribution and tumour localization of radiolabelled monoclonal antibody in a human tumour: nude mouse xenograft model

Abstract

A monoclonal antibody, against a colorectal carcinoma tumour-associated antigen, was radioiodinated and its biodistribution studied in comparison with that of control immunoglobulin in nude mice with colon carcinoma xenografts. Tumour localization of the antibody in comparison with normal tissues was poor, and in absolute terms more control IgG than antibody was present per gram of tumour. This failure to achieve localization could not be ascribed to poor immunoreactivity of the antibody nor to the failure of the xenografts to express the appropriate antigen. Analysis of serum from mice with xenografts showed the presence of circulating tumour-derived antigen. This serum-borne antigen was found to form immune complexes both in vitro and in vivo with the monoclonal antibody, and this complex formation is probably the limiting factor in tumour localization of the antibody. This is one of only few examples where mice with human tumour xenografts have levels of circulating antigen sufficient to perturb biodistribution of antibody. These findings are relevant to the biodistribution of monoclonal antibodies in the clinical situation, since circulating antigen is often found in cancer patients.