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Targeting Secreted Antigens for Precision Imaging and Therapy

Title: Targeting Secreted Antigens for Precision Imaging and Therapy
Date & Time: Jan 18, 2018 12:00 PM - Jan 19, 2018 1:00 PM
Location: Morton Room, 24-132 CHS

Hans David Ulmert, MD, PhD
Senior Research Scientist
The Steve Larson Lab
Memorial Sloan Kettering Cancer Center 

Highly specific and potent radioimmunotherapy (RIT) has previously been limited to targeting of cell surface proteins. I have successfully pioneered technology that enables targeting antigens secreted by luminal tissues opening a new class of cancer tissue-specific targets including widely used circulating biomarkers. This is a considerable advance over previous RIT efforts as disease specific secreted antigens are targeted, and radiotherapeutic doses are delivery intracellularly for maximum effect – as close to the nucleus as possible. This technology builds on recent advances in our understanding of neonatal Fc- receptor (FcRn) biology. This receptor selectively traffics IgG1/antigen complexes from the exterior of the cell to lysosome compartments, while unbound IgG1 are released back into the blood circulation. My antibody platform demonstrates exquisite affinity and specificity for androgen receptor (AR) governed enzymes hK2 and PSA, two well-characterized enzymes exclusively expressed in both prostate and AR-positive breast carcinomas. Despite targeting these secreted antigens, radio-conjugates of these antibodies anatomically localize and accumulate intracellularly in prostate and AR-positive breast cancer as revealed by PET and confocal microscopy. Applying this antibody-platform for RIT realizes molecularly specific delivery of cytotoxic radiotherapy to disseminated disease sites in commonly diagnosed malignancies in both men and women. The strategy is also motivated from a radiobiological standpoint; DNA-repair mechanisms up-regulate KLK2 and KLK3 as a response to genotoxic insults, resulting in a unique feed-forward up-regulation of the targeted enzymes. 

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