Macromolecular approaches for fluorescence-guided surgery of pancreatic cancer
Seminar with Aaron Mohs
Associate Professor - Department of Pharmaceutical Sciences
University of Nebraska Medical Center
Access the Zoom link for this virtual seminar here
Abstract: Surgical resection remains the only potentially curative option for pancreatic cancer (PC), but resections are complicated by infiltrative disease, proximity of critical vasculature, peritumoral inflammation, and dense stroma. Fluorescence-guided surgery (FGS) has emerged as a method to improve intraoperative detection of cancer and ultimately improve surgical outcomes. FGS relies on fluorophores, typically near infrared fluorophores, that are conjugated to molecules targeted to biomarkers that are overexpressed in the tumor or surrounding stroma. The targeted NIR probe is then visualized intraoperatively to guide complete resection of the tumor. In this talk, two macromolecular targeted approaches will be discussed. In the first part, selective accumulation of hyaluronic acid derived NIR conjugates will be described, including how tuning of dye and hyaluronic molecular weight can improve local contrast. In the second part of the talk, our recent work targeting mucin16 (MUC16) will be described. MUC16 is a glycoprotein overexpressed in 60-80% of PCs, yet this biomarker has not been fully investigated for FGS of this disease. Here, NIR fluorophore conjugates to a novel antibody, AR9.6, that targets MUC16, will be described. Investigations using multiple pancreatic cancer models with murine and humanized antibody conjugates will be described. In additional to surgical efficacy, preclinical biodistribution and safety studies will also be presented. Our results demonstrate that NIR fluorescent AR9.6 binds to MUC16, preferentially accumulates and identifies tumors with high tumor to background ratios, and does not exhibit long-term toxicity.
Dr. Aaron Mohs is an associate professor in the Department of Pharmaceutical Sciences, is a member of the Fred & Pamela Buffett Cancer Center, and shares a courtesy appointment in Biochemistry and Molecular Biology at the University of Nebraska Medical Center. Dr. Mohs received his B.A. in Chemistry from St. John’s University/College of St. Benedict (Collegeville, MN) and received his Ph.D. in Pharmaceutics and Pharmaceutical Chemistry at the University of Utah under Dr. Zheng-Rong Lu. Dr. Mohs then completed his postdoctoral fellowship in the joint Emory-Georgia Tech Department of Biomedical Engineering, as an Emory-Georgia Tech Center for Cancer Nanotechnology Excellence Distinguished Fellow with Dr. Shuming Nie. Dr. Mohs has an active, NIH-funded, collaborative research program on the development of fluorescent probes to guide the surgical resection of tumors, fluorescent sensor array technology that can rapidly detect and identify bacterial pathogens, and drug delivery systems to target multiple myeloma. Dr. Mohs is currently the President of the UNMC Faculty Senate, recently served as the Director of the Pharmaceutical Sciences Graduate Program, and actively serves on several College and University committees. Dr. Mohs is a recipient of the 2017 UNMC New Investigator award, 2019 UNMC Distinguished Scientist award, and, most recently, selected as a Fellow of the National Strategic Research Institute at the University of Nebraska. Prior to joining UNMC in 2015, Dr. Mohs was an assistant professor of Biomedical Engineering in the Wake Forest – Virginia Tech School of Biomedical Engineering and Sciences.