Fc Effector Bioassays for Rapid and Quantitative Measurement of ADCC and ADCP Mechanisms of Action
Poster Sep 19, 2017
Zhi-jie Jey Cheng, Rich Moravec, Aileen Paguio, Denise Garvin, Frank Fan, and Mei Cong
Drug developers and regulatory authorities recognize antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cell-mediated phagocytosis (ADCP) as important mechanisms of action (MOA) of therapeutic antibodies. Traditional ADCC and ADCP bioassays use primary cells, which are labor intensive and highly variable. Less variable, easy-to-use and consistent analysis of these important MOA is needed in drug development programs.
To meet this need, we have developed a suite of functional cell-based Fc Effector reporter bioassays for the following receptors:
• Human FcgRIIIa (V158 and F158 variants)
• Human FcgRIIa (H131 and R131 variants)
• Human FcgRI
• Mouse FcgRIV* & FcgRIII*
Each bioassay is provided in “thaw-and-use” format for a rapid and convenient workflow and further reduction in assay variability. In qualification studies according to ICH guidelines, the bioassays show specificity, accuracy, precision, and linearity enabling their use in antibody screening, characterization, stability and potency studies.
We utilized paired synthetic crRNAs coupled with our synthetic tracrRNA in cells transduced with lentiviral Cas9 to perform a functional knockout on hsa-miR-221. This three-part system (crRNA, tracrRNA and Cas9) has demonstrated efficient gene editing when used with only one guide RNA, but the goal was to use two crRNAs to remove the entire stem-loop.READ MORE
During early drug discovery, the study of metabolism plays an essential role in determining which drug candidates move forward into development and later stages. As an alternative to traditional Data Dependent Acquisition (DDA), the use of MSE/All Ions Fragmentation (AIF) has become common in metabolite identification workflows for the analysis of metabolic hot spots. Here we present a solution for analysis of MSE/AlF in metID studies.READ MORE