David Parkinson M.D.

President and Chief Executive Officer

Nodality

Dr. Jennie Mather is currently Senior Vice President of Stem Cell Research at Macrogenics, Inc. She has over thirty years of experience in cell culture and cell biology research and drug development. Dr. Mather was on the faculty of The Rockefeller University before joining Genentech in1984 where she worked in both Process Development and Discovery Research. She was involved in the development of 8 currently marketed recombinant protein products. Dr. Mather left Genentech in 1999 to found Raven biotechnologies, inc., a company focused on the discovery of drug targets and antibody therapeutics using an integrated cell biology.

PRESENTATION ABSTRACT:

Single cell resolution signaling network profiling as a basis for developing next-generation clinical predictive tests and biologically-targeted therapeutics in cancer and autoimmune disease

The cancer stem cell (CSC) hypothesis provides a foundation for understanding cancer development and carries significant implications relevant to drug discovery. By employing defined serum-free media conditions that are strongly selective for tissue specific stem/progenitor cells, we have been able to select distinct, minority cell populations, hereafter termed cancer stem-like cells (CSLC), from a number of solid tumors, including colon and lung. Nine lines have been obtained from patients with colon cancer and 4 from lung cancer patients. These lines have demonstrated self-renewal in vitro and in vivo. CSLCs implanted in NSG mice form tumors that are morphologically and phenotypically similar to the original patient’s tumor. Several lines have been cloned to show that single cells can give rise to fully differentiated, metastatic tumors. These CSLC are used as input in Macrogenics’ drug discovery platform, which raises antibodies to cell surface proteins then screens for binding and tumor-specificity on human tumor and normal tissue sections. Further screening for in vitro and in vivo activity is done in conventional and CSC-derived in vitro and in vivo models. Data suggest these CSLC lines provide valuable tools to study the biology of colon cancer stem cells and an opportunity for the development of strategies and therapeutics aimed at the detection and elimination of these cells.