Category: Assay Development and Screening

1151-B - In vitro Characterization of mAb Targeting a Glycosylphosphatidylinositol (GPI)-anchored Protein for Selection of Optimal Antibody Drug Conjugate Candidates

Monday, February 5, 2018
5:00 PM - 6:00 PM

ADCs are specific therapeutic monoclonal antibodies (mAb) chemically linked to cytotoxic payloads.   The design is aimed to provide selective delivery of cytotoxic payloads to tumors and to exert tumor targeted killing effects. For an ADC to be successful, it needs to bind to its target antigen on tumor cells, internalize via receptor-mediated endocytosis and be transported to the lysosome where subsequent intracellular processing of the ADC will release the biologically active drug.

Prior to the making of an ADC, an appropriate antibody clone with optimal binding and internalization into the cells needs to be selected.   Here we describe three in vitro characterization techniques to screen for various antibodies targeting glycosylphosphatidylinositol (GPI)-linked cell membrane protein. These in vitro  characterization techniques assess both anti-proliferation as well as the kinetics of binding and internalization by imaging cancer cells. To understand the biological relevance of these in vitro activities, an in vitro/in vivo comparison was explored. Overall, a mAb that has improved binding and prolonged internalization kinetics may yield improved efficacy and durability when conjugated to toxic payloads.

Josefa D. Chuh

Senior Scientific Researcher
South San Francisco, CA

Josefa dela Cruz Chuh, Senior Scientific Researcher - Genentech
Scientific Researcher, September 2005 – June 2016, and Senior Scientific Researcher, June 2016 to present at Genentech
Related Experience: Immunoassays for PK determination of various biologics, cellular functional assays as a screening tool for biologic discoveries, immunostaining/HTP imaging and Multiple reaction moniotring (MRM) LC/MS/MS for biologic characterization.