GlaxoSmithKline
Generic Name: Ofatumumab
Brand Name: Arzerra
Other Designation: HuMax-CD20, GSK1841157

Description: HuMax-CD20 is a human IgG1 monoclonal antibody (MAb) targeting the CD20 antigen on B cells for treatment of various types of leukemia or lymphoma.


Current as of: August 31, 2010

CD20

Investigators at the University of Virginia School of Medicine (Charlottesville, VA) and University Medical Center Utrecht, in the Netherlands, used spinning disk confocal fluorescent microscopy (SDCFM) to examine the real time dynamics of complement activation on CD20-positive cells, promoted by binding of rituximab and ofatumumab anti-CD20 MAb. Complement activation, mediated by these MAb, induced profound effects on Daudi and ARH77 cells. C3b deposition was readily demonstrable and substantial changes in morphology including rapid blebbing were evident. Most strikingly, long string-like structures were cast off the cells. Direct comparisons between rituximab and ofatumumab revealed several interesting differences. Ofatumumab readily promoted complement activation, C3b deposition, and killing of ARH77 cells, but rituximab-mediated C3b deposition was lower, and killing was close to background. In addition, maximum deposition of C3b fragments on ARH77 cells occurred considerably more rapidly for ofatumumab (30 seconds) than for rituximab (5 minutes). Consistent with these findings, binding of ofatumumab to ARH 77 cells in normal human serum (NHS) induced blebbing and generated streamers to a much greater degree (5 to 10-fold more) than in cells opsonized with rituximab and NHS. Moreover, for Daudi cells that were opsonized with the MAb on ice and then reacted with NHS and placed at 37C, ofatumumab induced streaming in 2 minutes, but rituximab-mediated streaming was not evident until at least 10 minutes. In summary, SDCFM allows for real time analysis of several distinct steps in MAb-mediated complement activation and killing of targeted cells. According to these results binding of ofatumumab to CD20-positive cells rapidly activates complement and produces profound changes in the cells, including the generation of streamers followed by cell death, in periods of 5 minutes or less (Taylor RP, etal, ASH07, Abs. 2345).