Enhancement of the activity of the complement inhibitor CDX-1135 by a monoclonal antibody

CDX-1135 (sCR1) is a soluble recombinant glycoprotein derived from the human complement regulatory protein Complement Receptor Type 1 (CR1, CD35, C3b/C4b receptor). CDX-1135 inhibits the classical, alternative and lectin pathways of the complement cascade, and is being evaluated for use in certain rare renal diseases involving dysregulated complement. A monoclonal antibody specific for CR1, designated 6B1.H12, appeared to enhance the inhibitory activity of CDX-1135 in an assay developed to detect anti-sCR1 antibodies with neutralizing activity in the alternative pathway. The 6B1.H12 antibody has been shown to bind a region of CR1 called long homologous repeat D (LHR-D). Because LHR-D does not contain a C3b or C4b binding site, it was expected that 6B1.H12 would have no neutralizing effect on CDX-1135 in an AP neutralization bioassay. We speculate that the enhancement of CDX-1135 activity at higher concentrations of 6B1.H12 may be due to the oligomerization of the CDX-1135, increasing the multivalency of b...