Abstract 4411: Novel internalizing human scFvs targeting pancreatic tumor cells residing in their natural tissue microenvironment

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the United States with a five-year survival rate of about 4%. Current diagnostic and therapeutic regimens are limited and ineffective. The goal of this project is to develop novel internalizing human antibodies that target pancreatic tumor cells residing within their natural tissue microenvironment, and possess the ability to translocate through the cell membrane to reach the inside of live tumor cells. Antibodies with these two properties, i.e., being able to target tumor cells in human tissue specimen and to penetrate live tumor cells, can in the future be used to develop minimally invasive imaging strategy for earlier detection and targeted therapy that requires efficient and specific accumulation of payloads inside tumor cells. To achieve this objective, we have selected a large naive phage antibody display library that we have recently constructed on microdissected human PDAC tissue specimens. We have identified a panel of internalizing human single chain antibodies (scFvs) that target pancreatic tumor cells in situ residing in their natural tissue microenvironment. Immunohistochemistry analysis showed that these scFvs bound to human PDAC, thereby recognizing clinically represented tumor antigens as opposed to cell line artifacts. All antibodies studied are internalized by PDAC cells in vitro. Using single photon emission computed tomography / computed tomography (SPECT/CT), we showed that technetium-labeled scFvs target human xenograft PDAC cells in vivo. Interestingly, a subset of these scFvs also target murine pancreatic tumor cell lines derived from transgenic PDAC mice, indicating that they target tumor epitopes conserved between human and mouse. Antibodies targeting tumor antigens across species would allow future imaging and therapy studies to be performed not only in xenograft but also transgenic PDAC models. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4411.