Abstract LB-001: Development and evaluation of a fluorescent antibody-drug conjugate for molecular imaging and targeted therapy of pancreatic cancer

Abstract

Developing new strategies to effectively diagnose and treat various types of cancer is paramount to increasing patient survival rates. Although chemotherapeutic small molecules are effective for some cancer types, they often have harmful side effects, resulting in significant damage to healthy tissue. Targeted therapy, where anti-cancer drugs are more precisely delivered to specific cells, has the potential to revolutionize chemotherapy, through increased localized effective doses with minimized systemic toxicity. Antibody-drug conjugates (ADCs) are one such class of targeted therapy biopharmaceuticals, employing the inherent specificity of antibodies as a targeting mechanism to yield a potent drug delivery system. In addition to being used as ADCs, antibody-conjugates are also commonly used as a highly effective tool for cancer typing and longitudinal treatment monitoring by immunohistochemistry staining or diagnostic imaging. However, antibody-conjugates used for tumor diagnosis and treatment are different molecules. Fluorescent dye labeling of therapeutic antibodies has been previously demonstrated for cancer imaging. However, therapeutic antibodies dual-labeled with both chemotherapeutic small molecules and fluorescent dyes has not been reported. Here, we demonstrate the development of a directly-labeled, fluorescent antibody-drug conjugate for simultaneous targeted drug delivery and in vivo molecular imaging of cancer. Our novel biopharmaceutical entity is a monoclonal antibody specific for a carcinoembryonic antigen (CEA) biomarker conjugated to an average of one molecule of paclitaxel and two molecules of a near-infrared fluorophore (DyLight 680-4xPEG). Preliminary data show that this fluorescent ADC selectively binds CEA positive cells and is cytotoxic using in vitro model systems. Ongoing studies using an in vivo mouse xenograft cancer model will demonstrate the utility of this fluorescent ADC as a new concurrent pancreatic cancer detection, monitoring and treatment technology. Citation Format: Steve Knutson, Erum Raja, Ryan Bomgarden, Marie Nlend, Aoshuang Chen, Ramaswamy Kalyanasundaram, Surbhi Desai. Development and evaluation of a fluorescent antibody-drug conjugate for molecular imaging and targeted therapy of pancreatic cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-001. doi:10.1158/1538-7445.AM2015-LB-001