Characterization of Prostate-Specific Membrane Antigen (PSMA) for Use in Therapeutic and Diagnostic Strategies against Prostate Cancer
Annual summary rept. 1 Jul 1999-30 Jun 2000
CLEVELAND CLINIC FOUNDATION OH
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Prostate-Specific Membrane Antigen PSMA is highly expressed in virtually 100 of prostate cancers and is expressed on the cell surface which makes it a useful target for both clinical and therapeutic strategies. However, there have been reports of PSMA expression in other, normal tissues, which could weaken its potential clinical use. We have shown that another gene very similar to PSMA existed, and the initial aim of this project was to clone this PSMA-Like gene. We cloned the PSMA-like gene, have shown that it is expressed in kidney and liver in humans, and that it has the same NAALADase activity that PSMA does. The gene is 97 identical to PSMA. The PSMA-like gene is not expressed in the prostate, nor is it expressed in prostate cancer or in tumor-associated neovasculature. We can now tailor anti-PSMA therapies to avoid tissues expressing the PSMA-like gene and subsequent patient toxicity. The second aim of this project was to isolate the most active portions of the PSMA enhancer for future therapeutic gene therapy use. We have developed a construct which has prostate specificity, driving expression of a suicide gene, which in future could be developed for use in therapeutic approaches.
- Medicine and Medical Research