rILYd4, a Human CD59 Inhibitor Enhances Complement Dependent Cytotoxicity of Ofatumumab against Rituximab-resistant B-cell Lymphoma Cells and Chronic Lymphocytic Leukemia
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rILYd4, a Human CD59 Inhibitor Enhances Complement Dependent Cytotoxicity of Ofatumumab against Rituximab-resistant B-cell Lymphoma Cells and Chronic Lymphocytic Leukemia
Published OnlineFirst September 14, 2011; doi: 10.1158/1078-0432.CCR-11-0647
http://clincancerres.aacrjournals.org/content/early/2011/09/14/1078-0432.CCR-11-0647
Citat:
It is widely accepted that OFA has much more potent CDC than RTX(18, 19).
Consistently, we found that OFA mediates much stronger CDC effects than RTX in all
cells. The more potent CDC effect mediated by OFA compared to RTX is attributed to
increased C1q binding and C3b(i) deposition on the target cells triggered. Previously,
Beum et al and Pawluczkowycz et al demonstrated that OFA triggers more C1q binding
and more C3b(i) deposition on these Daudi and Raji cells, leading to more MAC
attack(9, 23). These results were further confirmed by us with two other lymphoma cell
lines expressing high levels of CD59. The application of rILYd4 to OFA or RTXmediated
CDC specifically increases C9 deposition but not C1q binding and C3b(i)
deposition on the targeted cells. This result directly highlights the specificity of rILYd4
activity, the inhibition of anti-MAC activity of CD59.
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