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Clinical Trials of Cancer Therapies Targeting Prostate-Specific Membrane Antigen

[ Vol. 2 , Issue. 3 ]

Author(s):

William C. Olson, Warren D.W. Heston and Ayyappan K. Rajasekaran   Pages 182 - 190 ( 9 )

Abstract:


Prostate cancer is the most common non-cutaneous cancer of men in the United States and represents their second-leading cause of cancer-related death. Metastatic disease is largely resistant to conventional chemotherapies, and targeted therapies are urgently needed. Prostate-specific membrane antigen (PSMA) is a prototypical cell-surface marker of prostate cancer. PSMA is an integral, nonshed, type 2 membrane protein with abundant and nearly universal expression in prostate carcinoma, but has limited extra-prostatic expression. In addition, PSMA is expressed in the neovasculature of other solid tumors. These findings have spurred development of PSMA-targeted therapies for cancer, and first-generation products have entered clinical testing. Vaccine approaches have included recombinant protein, nucleic acid and cell-based strategies, and anti-PSMA immune responses have been demonstrated in the absence of significant toxicity. Therapy with drug-conjugated and radiolabeled antibodies has yielded objective clinical responses as measured by reductions in serum prostate-specific antigen and/or imageable tumor volume. However, responses were observed in a minor fraction of patients and at doses near the maximum tolerated dose. Overall, these initial studies have provided measured proof of concept for PSMAbased therapies, and second-generation antibody and vaccine products may hold the key to exploit PSMA for molecularly targeted therapy of prostate and other cancers.

Keywords:

Prostate-specific membrane antigen, prostate cancer, immunotherapy, antibody-drug conjugate

Affiliation:

Nemours Center for Childhood Cancer Research, A.I. duPont Hospital for Children, 1600 Rockland Road, Wilmington, DE; USA.



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