DIMERIC RECOMBINANT IGA DIRECTED AGAINST CARCINOEMBRYONIC ANTIGEN, A NOVEL TOOL FOR CARCINOMA LOCALIZATION

Carcinoembryonic antigen (CEA) has been shown to be one of the best ma rkers for in vivo tumor targeting of radiolabeled antibodies, despite the fact that it is localized predominantly at the apical side of huma n colon carcinoma cells within the fairly closed pseudolumen structure s formed by these tumors. Due to this particular histological localiza tion, a large proportion of the CEA molecules may remain inaccessible to the intravenously injected radiolabeled anti-CEA antibodies of IgG isotype, which are widely used in the clinic. In order to improve targ eting, we made a recombinant dimeric IgA, which should have the capaci ty to translocate from the basolateral to the apical side of the pseud olumen formed by colon carcinoma cells after binding to the polyIg rec eptor (pIgR). A genomic chimeric mouse-human IgA, construct was made u sing one of our most specific anti-CEA hybridomas, CE-25. The chimeric IgA (chIgA) was expressed in the Sp2/0 myeloma cell line. The secrete d recombinant antibody was found to consist mostly of a dimeric form o f IgA with a molecular weight of about 350 kDa. The dimeric chIgA was shown to translocate efficiently in vitro across a monolayer of epithe lial cells expressing the pIgR and to retain full CEA binding activity .