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Antibody Drug Carrier for Immunotherapy of Superficial Bladder Cancer: Ultrastructural Studies¹

Department of Pathology, University of Toronto, Toronto, Ontario, Canada [E. d. H., W. H., S. H., Y. W., R. M., G. B. A. T., H. C.]; Centre de Recherche de l'Hotel-Dieu, Universite Laval, Quebec City, Province Quebec, Canada [Y. F.]; Department of Surgery, University of Toronto, Toronto, Ontario, Canada [J. G. C.]; and Occupational and Environmental Health Unit, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada [B. C. K. C.]

Superficial bladder cancer represents a promising target for intravesical, antibody-guided therapy. The construction of an optimum antibody-cytotoxic drug conjugate depends mostly on the appropriate selection of a monoclonal antibody (mAb). We have used immunogold labeling and SEM to specifically map the distribution of antigens expressed on three bladder cancer cell lines and on the luminal surface of biopsies from human transitional cell carcinoma of various grades and from normal bladder mucosa. The 48–127 mAb, which recognizes a M_r 54,000 surface glycoprotein (gp54), was found to be very promising as a potential drug carrier. This antibody reacts with the surface of cells from low- and high-grade tumors; it does not react with the normal urothelium. Labeling of normal bladder mucosa was observed, however, on microvillous intermediate urothelial cells occasionally exposed by small areas of desquamation. The 48–127 mAb could target drugs to all areas of transformed urothelium while avoiding drug delivery to the normal, undesquamated bladder mucosa. Kinetics of gp54/48–127/gold complexes were tested in vitro with T24 and RT4 human bladder carcinoma cell lines incubated in the presence of the 48–127 mAb directly conjugated with 17.7-nm gold particles. Internalization of the gp54/48–127/gold complex was readily demonstrated by transmission electron microscopy. These results suggest that the 48–127 mAb represents a valuable drug carrier for intravesical therapy, allowing specific tumor targeting and internalization of various cytotoxic agents.

¹ This investigation was supported by Research Grants 1214 (to E. D. H.) and 1646 (to Y. F.) from the National Cancer Institute of Canada and by a grant from the Cancer Research Society (to B. C. K. C.).

² To whom requests for reprints should be addressed, at Banting Institute, 100 College Street, Toronto, Ontario M5G 1L5, Canada.

³ Scientist of the Medical Research Council of Canada.

Received 3/ 6/91. Accepted 3/19/92.