19:10 - 21:00
Room: Ishikawa Ongakudō Interchange Hall
Poster Session
A Novel System for the Quantification of the ADCC Activity of Therapeutic Antibodies
Michael Gerard tovey1, Christophe Lallemand2, Feifei Liang2, Flore Staub2, Maud Simansour2, Benoit Vallette2, Lue Huang2, Rosa Ferrando-Miguel2
1Laboratory of Biotechnology & Applied Pharmacology, Ecole Normale Supérieure de Cachan,, Cachan, France, 2Biomonitor SAS, Villejuif Bio Park, 1 Mail du Professeur Georges Mathé, Villejuif, France

Novel ADCC effector cells expressing the V or F-variant of FcgRIIIa (CD16a) and firefly luciferase under the control of a chimeric promoter incorporating recognition sequences for the principal transcription factors involved in FcgRIIIa signal transduction, together with novel target cells over-expressing a constant high level of the specific antigen recognized by rituximab, trastuzumab, cetuximab, infliximab, adalimumab or etanercept, confer improved sensitivity, specificity, and dynamic range in an ADCC assay relative to effector cells expressing a NFAT regulated reporter-gene and wildtype target cells. The effector cells also contain a normalization gene rendering ADCC assays independent of cell number or serum matrix effects. The novel effector and target cells in a frozen thaw-and-use format exhibit low vial-to-vial and lot-to-lot variation in their performance characteristics reflected by CVs of 10% or less. Homologous control target cells in which the specific target gene has been invalidated by genome editing providing an ideal control and a means of correcting for non-specific effects observed with certain samples of human serum. The novel effector cells and target cells expressing non-cleavable membrane-bound TNFa have been used to quantify ADCC activity in serum from patients with Crohn’s disease treated with infliximab and to relate ADCC activity to drug levels.


Reference:
Mo-P9-2
Session:
Poster Session 9 “Anti-cytokine therapy for inflammatory human diseases”
Presenter/s:
Michael Gerard tovey
Presentation type:
Poster Presentation
Room:
Ishikawa Ongakudō Interchange Hall
Date:
Monday, 30 October 2017
Time:
19:10 - 21:00
Session times:
19:10 - 21:00