title: Prostate stem cell antigen as therapy target: tissue expression and in vivo efficacy of an immunoconjugate.
abstract: 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.
authors: Department of Pathology, Genentech, Inc., South San Francisco, California 94080, USA.
authors: Sarajane
authors: S
authors: Ross
authors: Susan D
authors: SD
authors: Spencer
authors: Ilona
authors: I
authors: Holcomb
authors: Christine
authors: C
authors: Tan
authors: JoAnne
authors: J
authors: Hongo
authors: Brigitte
authors: B
authors: Devaux
authors: Linda
authors: L
authors: Rangell
authors: Gilbert A
authors: GA
authors: Keller
authors: Peter
authors: P
authors: Schow
authors: Rita M
authors: RM
authors: Steeves
authors: Robert J
authors: RJ
authors: Lutz
authors: Gretchen
authors: G
authors: Frantz
authors: Kenneth
authors: K
authors: Hillan
authors: Franklin
authors: F
authors: Peale
authors: Patti
authors: P
authors: Tobin
authors: David
authors: D
authors: Eberhard
authors: Mark A
authors: MA
authors: Rubin
authors: Laurence A
authors: LA
authors: Lasky
authors: Hartmut
authors: H
authors: Koeppen
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000493:pharmacokinetics / Q000494:pharmacology*; D000951:Antigens, Neoplasm; D005260:Female; D058851:GPI-Linked Proteins; D006801:Humans; D007116:Immunization, Passive / Q000379:methods; D000922:Immunotoxins / Q000493:pharmacokinetics / Q000494:pharmacology; D017403:In Situ Hybridization; D008297:Male; D008453:Maytansine / Q000493:pharmacokinetics / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D058851:GPI-Linked Proteins; D000922:Immunotoxins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C110843:PSCA protein, human; C504399:Psca protein, mouse; D008453:Maytansine