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[Cancer Research 62, 2546-2553, May 1, 2002]
© 2002 American Association for Cancer Research

Experimental Therapeutics

Prostate Stem Cell Antigen as Therapy Target

Tissue Expression and in Vivo Efficacy of an Immunoconjugate

Sarajane Ross1, Susan D. Spencer1, Ilona Holcomb, Christine Tan, JoAnne Hongo, Brigitte Devaux, Linda Rangell, Gilbert A. Keller, Peter Schow, Rita M. Steeves, Robert J. Lutz, Gretchen Frantz, Kenneth Hillan, Franklin Peale, Patti Tobin, David Eberhard, Mark A. Rubin, Laurence A. Lasky and Hartmut Koeppen2

Departments of Pathology [S. R., I. H., G. F., K. H., F. P., P. T., D. E., H. K.], Molecular Oncology [S. D. S., L. A. L.], Antibody Technology [C. T., J. H., B. D.], Toxicology [L. R., G. A. K.], and Immunology [P. S.], Genentech, Inc., South San Francisco, California 94080; ImmunoGen, Inc., Cambridge, Massachusetts 02139 [R. M. S., R. J. L.]; and Department of Pathology and Urology, University of Michigan, Ann Arbor, Michigan 48109 [M. A. R.]

We conducted an expression analysis of prostate stem cell antigen (PSCA)in normal urogenital tissues, benign prostatic hyperplasia (n = 21), prostatic intraepithelial neoplasia (n = 33), and primary (n = 137) and metastatic (n = 42) prostate adenocarcinoma, using isotopic in situ hybridization on tissue microarrays. In normal prostate, we observe PSCA expression in the terminally differentiated, secretory epithelium; strong expression was also seen in normal urothelium. Forty-eight percent of primary and 64% of metastatic prostatic adenocarcinomas expressed PSCA RNA. Our studies did not confirm a positive correlation between level of PSCA RNA expression and high Gleason grade. We characterized monoclonal anti-PSCA antibodies that recognize PSCA expressed on the surface of live cells, are efficiently internalized after antigen recognition, and kill tumor cells in vitro in an antigen-specific fashion upon conjugation with maytansinoid. Unconjugated anti-PSCA antibodies demonstrated efficacy against PSCA-positive tumors by delaying progressive tumor growth in vivo. Maytansinoid-conjugated antibodies caused complete regression of established tumors in a large proportion of animals. Our results strongly suggest that maytansinoid-conjugated anti-PSCA monoclonal antibodies should be evaluated as a therapeutic modality for patients with advanced prostate cancer.




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Copyright © 2002 by the American Association for Cancer Research.