Characterization of a Next Generation Anti-CD52 Antibody (S20.006)
2015
OBJECTIVE: To assess the in vitro and in vivo activity of GZ402668, a novel anti-
CD52antibody. BACKGROUND:
Alemtuzumabis an anti-
CD52humanized monoclonal antibody that causes depletion of circulating lymphocytes followed by a distinctive pattern of
repopulation. It is approved for the treatment of relapsing forms of multiple sclerosis (MS) in over 30 countries. A next-generation anti-
CD52antibody is currently being developed to potentially decrease immunogenicity, improve the infusion-associated reaction (IAR) profile, and explore the
subcutaneous routeof administration while maintaining efficacy. DESIGN/METHODS: In vitro activity of GZ402668 was analyzed in both antibody-dependent cell-mediated
cytolysis(ADCC) and complement-dependent
cytolysis(CDC) assays as well as in a human whole blood cytokine release assay. In addition, the immunogenicity profile of GZ402668 was assessed using in vitro assays. Pharmacology studies were carried out in the human
CD52transgenic mouse to characterize the depletion profile and lymphocyte
repopulationkinetics. RESULTS: GZ402668 mediated in vitro lymphocyte depletion by both ADCC and CDC comparable to
alemtuzumab. In the whole blood assay, GZ402668 induced a significantly lower cytokine response than
alemtuzumabfor most concentrations of test article. In an in vitro immunogenicity assay, 70[percnt] of donors responded to
alemtuzumabpeptides, whereas only 30[percnt] responded to GZ402668. Subcutaneous and intravenous administration of GZ402668 to huCD52 transgenic mice resulted in dose-dependent lymphocyte depletion followed by lymphocyte
repopulationkinetics comparable to
alemtuzumab. CONCLUSIONS: GZ402668 is a next-generation anti-
CD52antibody with lymphocyte-depleting activity similar to that of
alemtuzumab. GZ402668 displays reduced cytokine release in a human whole blood assay, suggesting a potentially improved IAR profile as well as predicted reduced immunogenicity. A phase 1 study including intravenous and subcutaneous administration in MS patients is currently planned. Study Supported by: Genzyme, a Sanofi company Disclosure: Dr.
Sidershas received personal compensation for activities with Genzyme Corporation as an employee. Dr. Greene has received personal compensation for activities with Genzyme as an employee. Dr. McVie-Wylie has received personal compensation for activities with Genzyme as an employee. Dr. Bailey has received personal compensation for activities with Genzyme as an employee. Dr. Dhawan has received personal compensation for activities with Genzyme as an employee. Dr. Boutin has received personal compensation for activities with Genzyme as an employee. Dr. Best has received personal compensation for activities with Genzyme as an employee. Dr. Lawendowski has received personal compensation for activities with Genzyme as an employee. Dr. Turner has received personal compensation for activities with Genzyme Corporation as an employee. Dr. Roberts has received personal compensation for activities with Genzyme Corporation as an employee. Dr. Kaplan has received personal compensation for activities with Genzyme as an employee. Dr. Sendak has received personal compensation for activities with Genzyme Corporation as an employee.
Keywords:
-
Correction
-
Source
-
Cite
-
Save
0
References
0
Citations
NaN
KQI