Development of PCSA-Targeted Minibodies for Imaging of Prostate Cancer
Annual rept. 1 Aug 2008-31 Jul 2009
CALIFORNIA UNIV LOS ANGELES
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The humanized antibody to prostate stem cell antigen PSCA, a cell surface marker on prostate cancer cells, combined with PET scanning was developed to image prostate tumor. The antibody was successful in preclinical model, although humanization caused a loss of affinity relative to the parental monoclonal antibody. To improve the imaging agent, multiple versions of humanized PSCA antibody fragments were created and subsequently tested for their abilities to image in vivo using micro-PET, with the goal to eventually detect distant metastases. Both the engineered minibodies and diabodies were able to successfully detect tumor, and the affinity that was decreased upon humanization was improved. Experiments are ongoing to characterize the affinity matured variant of the minibodies, therefore a lead agent has not been chosen, but this is expected to happen in the next year. On the other hand, a human PSCA knockin mouse model was generated, verified and maintained. This genetically engineered murine line is being expanded and will be used to cross to a known model of mouse prostate cancer in the next year.
- Anatomy and Physiology
- Medicine and Medical Research