Plenary: Next Frontier, Monday
Plenary: Next Frontier
Presentation Authors: mohammad siddiqui*, Reema Railkar, Thomas Sanford, Peter Choyke, Hisataka Kobayashi, Piyush Agarwal, bethesda, MD
Introduction: Bladder cancer (BC) is heterogeneous, expressing various cell surface targets, such as EGFR and Her2. Photoimmunotherapy (PIT) involves antibodies (Abs) conjugated to a photoabsorber (PA), IR Dye 700Dx, and then activated by Near infra-red light (NIR) to specifically target tumors. Our lab has previously shown that tumors expressing high levels of EGFR can be efficiently targeted with PIT. However, PIT is less effective when a tumor lacks “overwhelming” expression of a single target. Here, we present a novel, combinatorial PIT approach for such tumors expressing EGFR and Her2, using Panitumumab-IR700 (PanIR700) and Trastuzumumab-IR700 (TraIR700) antibodies, respectively.
Methods: BC cell lines were analyzed for expression of EGFR and Her2 using flow cytometery. Concurrent and optimal binding of both PA-labeled Abs were determined using flow cytometery. NIR LD50 of multiple treatment regimens were determined to analyze in vitro efficacy of combination PIT.
Results: The SW780 and RT112 cell lines showed low to moderate expression of EGFR and Her2. The EGFR expression was 143 fold higher in SW780 and 83 fold higher in RT112 over the isotype control. The Her2 expression was 42 fold higher in SW780 and 27 fold higher in RT112 over the isotype control. Hence, the ratio of cell surface EGFR to Her2 expression in both cell lines was about 3:1. For SW780, NIR LD50 was 28.66 J/cm2 for the combination PIT compared to 71.55 J/cm2 for the PanIR700 alone therapy. The NIR LD50 for RT112 was 14.66 J/cm2 for the combination PIT, with LD50 for PanIR700 alone therapy indeterminate from insufficient cell death. In both cases, the LD50 for TraIR700 alone therapy could not be determined from lack of sufficient cell death.
Conclusions: PIT is a new targeted treatment for bladder cancer that can be effectively used either locally or for metastatic lesions accessible by the NIR light. We demonstrate a novel and promising approach to treating BC by selectively inducing cell death in BC cell lines with low to moderate expression of cell surface markers of EGFR and Her2 using combination PIT. This will be further evaluated in a xenograft model.
Source Of Funding: Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. This research is also made possible through the NIH Medical Research Scholars Program, a public-private
partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation, the American Association for Dental Research, the Colgate-Palmolive Company, Genentech, and other private donors. For a complete list, visit the foundation website at http://www.fnih.org
National Institutes of Health
I am Rashid Siddiqui, currently a Medical Reseach Scholars Program (MRSP) scholar in Dr. Piyush Agarwal's lab at the National Instittutes of Health. I attend medical school at the University of Wisconsin School of Medicine and Public Health (UWSMPH) and have completed three out of four years. I attended University of California, Berkeley for undergraduate where I majored in Molecular and Cell Biology with an emphasis in Immunology. Thereafter, I spent 3 years doing basic science research in neurology at Stanford University before attending UWSMPH for medical school. I am interested in purusing urology residency with the hope of doing a urologic oncology fellowship afterwards.
Tuesday, May 16
9:30 AM – 11:30 AM