Development of a Novel Method to Detect Prostate Cancer Circulating Tumor Cells (CTCs) Based on Epithelial-Mesenchymal Transition Biology
Final rept. 10 Sep 2012-9 Sep 2014
DUKE UNIV DURHAM NC
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The purpose of this DOD NIA is to develop a novel method to detect circulating tumor cells CTCs from men with metastatic castration resistant prostate cancer CRPC based on a range of CTC phenotypes. The novel method employs a nanoparticle polymersome that contains near-infrared emissive porphyrins and permits antibody conjugation for target engagement and flow sorting in the infrared spectrum for specificity. We are developing near infrared emissive polymersomes NIR-EPs that contain antibodies to EpCAM, N-cadherin, OB-cadherin, and PSMA which permit the isolation and enumeration ev vivo of CTCs bearing these antigens in the circulation of men with CRPC. These specialized CTC detection nanoparticles permit the isolation of specific CTC phenotypes including epithelial, mesenchymal, and prostate cancer specific targets. In year 2 we have continued to optimize the methodology and chemistry for the creation of these NIR-EPs, including chemical synthesis, antibody conjugation, optimal reagents and processing, positive and negative control cell applications, and methods for red cell lysis, leukocyte depletion, and flow sorting of CTCs in the infrared spectrum. Challenges have included specificity due to antibody affinity during conjugation. This work is ongoing in the Therien laboratory to provide a clinical reagent for the ex vivo capture and identification of CTCs without binding to leukocytes nonspecifically. A 6 month no cost extension was requested to continue this optimization process.
- Medicine and Medical Research