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Development of 5D3 mAb and USPIO-Based Theranostics for Image-Guided Prostate Cancer Therapy


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Prostate cancer (PC) is the most common cancer in men and associated with the second highest cancer related mortality. Therefore, new treatment strategies including novel drugs and drug delivery systems are urgently needed for PC therapy. Prostate-specific membrane antigen (PSMA) is overexpressed in almost all PC. PSMA is used as a biomarker for targeted drug delivery and diagnostic imaging of PC. 5D3 mAb is a novel antibody with better circulation half-time, higher binding affinity with PSMA, and fast internalization kinetics compared to commercially available anti-PSMA mAbs. In this study, we have been using ultra-small superparamagnetic iron oxide (USPIO) nanoparticles as the drug delivery platform to delivery DM1. During last two years, we have successfully developed a USPIO-5D3-DM1conjugates and studied them in preclinical mouse models. Novel acidic linker (AL) was developed for the conjugation of DM1 with USPIO. We have developed aHPLC method and AL linker was tested for the controlled release of drugs in a dextran platform. In the third year, we will conjugate DM1 with USPIO-5D3 system using AL linker, labeled them with 89Zr to image by PET-MRI. Therapeutic and toxicological studies will be conducted in human PC xenograft mouse models.



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