Figure 5
Effect of factor H downregulation on cetuximab-mediated complement activation. A, A549 cells were incubated with NHS and cetuximab in the presence or absence of OX24, an antibody that inhibits the binding of factor H to surface-bound C3b. Deposition of C3-related fragments, evaluated by flow cytometry, significantly increased in the presence of OX24 (*, P < 0.05). Data represent mean + SEM. B, Xenografts of A549 cells deficient in factor H (FH siRNA) were grown in nude mice until they reached ~250 mm3 (n = 8). Half of the mice were treated with cetuximab, and the other half with PBS. The same experiment was conducted in A549 cells stably transfected with a scramble siRNA (control siRNA). Results shown represent mean ± SEM. The antitumor activity of cetuximab was significantly higher in factor H-deficient cells than in cells transfected with a control siRNA (*, P < 0.05). C, representative examples of the deposition of C3-related fragments in the explanted tumors.