Abstract A06: Identification of tumor-specific antibodies using phage display selections on pancreatic ductal organoids

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with a five year survival rate at 6%. The high mortality of this disease is associated with its late diagnosis. Developing accurate means of early detection will allow for curative surgery and significantly improve patient outcomes. Monoclonal antibodies against tumor-associated neoepitopes are promising tools for identifying novel biomarkers due to their exquisite specificity. To generate antibodies specific to pancreatic tumor cells, we have adapted previously established screening methods with synthetic phage displayed Fab libraries to the pancreatic ductal organoid system, a recently developed ex vivo platform for culturing both normal and malignant pancreatic tissue. This antibody screen employs negative selection of Fabs binding normal organoids to eliminate those cell surface markers elevated during normal ductal cell proliferation, a state similar to the proliferation observed in the pancreas during inflammatory conditions. This is significant because the ability of novel biomarkers to accurately detect pancreatic cancer depends on their capacity to distinguish PDAC from benign diseases of the pancreas. Using this method, we have isolated five unique Fabs that preferentially bind cell surface antigens on tumor but not normal organoids derived from human PDAC and non-diseased patients respectively. Characterization of the cognate antigens of these antibodies and validation of their binding to human tissue are ongoing. We demonstrate that pancreatic ductal organoids provide a systematic platform to screen antibody libraries for the discovery of biomarkers specific to the neoplastic state. Citation Format: Tobiloba E. Oni, Carmelita Bautista, Bryce Nelson, David A. Tuveson.{Authors}. Identification of tumor-specific antibodies using phage display selections on pancreatic ductal organoids. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr A06.