Genmab — Maj 2014
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http://bloodjournal.org/content/123/12/1957?rss=1&variant=short jo det er Ibrutinibs blokering af ADCC, der er problemet
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I har nok ret, men det er skrevet, så jeg ikke helt forstår det http://files.shareholder.com/downloads/AMDA-KPIBN/3189490857x0x757121/F224E13F-4143-4E97-B339-D03AD9E14257/EHA2014-Ofatumumab-Ibrutinib-Prelinical-DaRoit.pdf
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Genmab har lagt alle abstracts på hjemmesiden nu http://ir.genmab.com/downloads.cfm
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The combination of ibrutinib with type II CD20 mAbs does not lead to enhanced direct
cytotoxicity in vitro. In contrast, it inhibits all cell-mediated cytotoxic mechanisms of action of CD20 antibodies and
has minor effects on CDC. Idelalisib has similar, albeit weaker, inhibitory activity on the cell-mediated effector
mechanisms of CD20 mAbs. The design of combined treatment schedules with these kinase inhibitors and anti-
CD20 antibodies should therefore consider the multiple negative interacti -
Key Findings:
• GA101 activates ADCC in cultured human B-cell cancer cells using human
PBMCs or an engineered cell line that expresses FcγRIIIa (Report 1025241,
reviewed below). The ADCC activity is greater in side-by-side comparisons with
rituximab but the magnitude of differences varies with the concentrations of
mAbs used. The addition of nonspecific human IgGs reduces the ADCC
activated by either GA101 or rituximab. -
• The ability of GA101, rituximab and ofatumumab to activate ADCP was
compared using M1 and M2c macrophages generated from human monocytederived
macrophages.14 No significant differences were observed between the
three antibodies with respect to ADCP, in the presence or absence of competing
endogenous human IgGs.
• GA101 binds to either FcγRIIIa 158V/F variant with greater affinity than rituximab -
http://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/125486Orig1s000PharmR.pdf Gazyva bruger også ADCC - så vidt jeg forstod på det ....
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ja men Gazyva i høje koncentrationer = fucking giftigt
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og Arzerra er jo stadig langt bedre på CDC end Rituxan?
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