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

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[Technical Report, Annual Report]

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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 includingnovel drugs and drug delivery systems are urgently needed for PC therapy. Prostate-specific membrane antigen PSMA is overexpressed in almost all PC. PSMA isused 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 affinitywith PSMA, and fast internalization kinetics compared to commercially available anti-PSMA mAbs. In this study, we have been using ultra-small superparamagneticiron 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 systemusing 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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[A, Approved For Public Release]