This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ross, S. Articles by Koeppen, H. Search for Related Content PubMed PubMed Citation Articles by Ross, S. Articles by Koeppen, H.

Prostate Stem Cell Antigen as Therapy Target

Tissue Expression and in Vivo Efficacy of an Immunoconjugate

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.

This article has been cited by other articles:

				A. C. Siva, M. A. Wild, R. E. Kirkland, M. J. Nolan, B. Lin, T. Maruyama, F. Yantiri-Wernimont, S. Frederickson, K. S. Bowdish, and H. Xin Targeting CUB Domain-Containing Protein 1 with a Monoclonal Antibody Inhibits Metastasis in a Prostate Cancer Model Cancer Res., May 15, 2008; 68(10): 3759 - 3766. [Abstract] [Full Text] [PDF]

				M. de la Luz Garcia-Hernandez, A. Gray, B. Hubby, O. J. Klinger, and W. M. Kast Prostate Stem Cell Antigen Vaccination Induces a Long-term Protective Immune Response against Prostate Cancer in the Absence of Autoimmunity Cancer Res., February 1, 2008; 68(3): 861 - 869. [Abstract] [Full Text] [PDF]

				N. Ishikawa, A. Takano, W. Yasui, K. Inai, H. Nishimura, H. Ito, Y. Miyagi, H. Nakayama, M. Fujita, M. Hosokawa, et al. Cancer-Testis Antigen Lymphocyte Antigen 6 Complex Locus K Is a Serologic Biomarker and a Therapeutic Target for Lung and Esophageal Carcinomas Cancer Res., December 15, 2007; 67(24): 11601 - 11611. [Abstract] [Full Text] [PDF]

				P. M. Challita-Eid, K. Morrison, S. Etessami, Z. An, K. J. Morrison, J. J. Perez-Villar, A. B. Raitano, X.-C. Jia, J. M. Gudas, S. B. Kanner, et al. Monoclonal Antibodies to Six-Transmembrane Epithelial Antigen of the Prostate-1 Inhibit Intercellular Communication In vitro and Growth of Human Tumor Xenografts In vivo Cancer Res., June 15, 2007; 67(12): 5798 - 5805. [Abstract] [Full Text] [PDF]

				M. d. l. L. Garcia-Hernandez, A. Gray, B. Hubby, and W. M. Kast In vivo Effects of Vaccination with Six-Transmembrane Epithelial Antigen of the Prostate: A Candidate Antigen for Treating Prostate Cancer Cancer Res., February 1, 2007; 67(3): 1344 - 1351. [Abstract] [Full Text] [PDF]

				J. Yang, H. Chen, I. R. Vlahov, J.-X. Cheng, and P. S. Low Evaluation of disulfide reduction during receptor-mediated endocytosis by using FRET imaging PNAS, September 12, 2006; 103(37): 13872 - 13877. [Abstract] [Full Text] [PDF]

				C. D. Austin, X. Wen, L. Gazzard, C. Nelson, R. H. Scheller, and S. J. Scales Oxidizing potential of endosomes and lysosomes limits intracellular cleavage of disulfide-based antibody-drug conjugates PNAS, December 13, 2005; 102(50): 17987 - 17992. [Abstract] [Full Text] [PDF]

				Z. Gu, J. Yamashiro, E. Kono, and R. E. Reiter Anti-Prostate Stem Cell Antigen Monoclonal Antibody 1G8 Induces Cell Death In vitro and Inhibits Tumor Growth In vivo via a Fc-Independent Mechanism Cancer Res., October 15, 2005; 65(20): 9495 - 9500. [Abstract] [Full Text] [PDF]

				R. Parry, D. Schneider, D. Hudson, D. Parkes, J.-A. Xuan, A. Newton, P. Toy, R. Lin, R. Harkins, B. Alicke, et al. Identification of a Novel Prostate Tumor Target, Mindin/RG-1, for Antibody-Based Radiotherapy of Prostate Cancer Cancer Res., September 15, 2005; 65(18): 8397 - 8405. [Abstract] [Full Text] [PDF]

				J. S. Lam, J. Yamashiro, I. P. Shintaku, R. L. Vessella, R. B. Jenkins, S. Horvath, J. W. Said, and R. E. Reiter Prostate Stem Cell Antigen Is Overexpressed in Prostate Cancer Metastases Clin. Cancer Res., April 1, 2005; 11(7): 2591 - 2596. [Abstract] [Full Text] [PDF]

				P. Carter, L. Smith, and M. Ryan Identification and validation of cell surface antigens for antibody targeting in oncology Endocr. Relat. Cancer, December 1, 2004; 11(4): 659 - 687. [Abstract] [Full Text] [PDF]

				D. Dornan, S. Bheddah, K. Newton, W. Ince, G. D. Frantz, P. Dowd, H. Koeppen, V. M. Dixit, and D. M. French COP1, the Negative Regulator of p53, Is Overexpressed in Breast and Ovarian Adenocarcinomas Cancer Res., October 15, 2004; 64(20): 7226 - 7230. [Abstract] [Full Text] [PDF]

				D. E.H. Afar, V. Bhaskar, E. Ibsen, D. Breinberg, S. M. Henshall, J. G. Kench, M. Drobnjak, R. Powers, M. Wong, F. Evangelista, et al. Preclinical validation of anti-TMEFF2-auristatin E-conjugated antibodies in the treatment of prostate cancer Mol. Cancer Ther., August 1, 2004; 3(8): 921 - 932. [Abstract] [Full Text] [PDF]

				E. R. Boghaert, L. Sridharan, D. C. Armellino, K. M. Khandke, J. F. DiJoseph, A. Kunz, M. M. Dougher, F. Jiang, L. B. Kalyandrug, P. R. Hamann, et al. Antibody-Targeted Chemotherapy with the Calicheamicin Conjugate hu3S193-N-Acetyl {gamma} Calicheamicin Dimethyl Hydrazide Targets Lewisy and Eliminates Lewisy-Positive Human Carcinoma Cells and Xenografts Clin. Cancer Res., July 1, 2004; 10(13): 4538 - 4549. [Abstract] [Full Text] [PDF]

				J. V. Tricoli, M. Schoenfeldt, and B. A. Conley Detection of Prostate Cancer and Predicting Progression: Current and Future Diagnostic Markers Clin. Cancer Res., June 15, 2004; 10(12): 3943 - 3953. [Abstract] [Full Text] [PDF]

				V. Bhaskar, D. A. Law, E. Ibsen, D. Breinberg, K. M. Cass, R. B. DuBridge, F. Evangelista, S. M. Henshall, P. Hevezi, J. C. Miller, et al. E-Selectin Up-Regulation Allows for Targeted Drug Delivery in Prostate Cancer Cancer Res., October 1, 2003; 63(19): 6387 - 6394. [Abstract] [Full Text] [PDF]

				P. S. NELSON Identifying Immunotherapeutic Targets for Prostate Carcinoma through the Analysis of Gene Expression Profiles Ann. N.Y. Acad. Sci., December 1, 2002; 975(1): 232 - 246. [Abstract] [Full Text] [PDF]

				C. P. Tran, C. Lin, J. Yamashiro, and R. E. Reiter Prostate Stem Cell Antigen Is a Marker of Late Intermediate Prostate Epithelial Cells Mol. Cancer Res., December 1, 2002; 1(2): 113 - 121. [Abstract] [Full Text] [PDF]