- Simple and reliable methods for evaluating the inhibitory effects of drug candidates on complement activation are essential for preclinical development.
- Using an immortalized porcine aortic endothelial cell line (iPEC) as target, this study evaluated the feasibility and effectiveness of an in vitro xenoantibody-mediated complement-dependent cytotoxicity (CDC) model for evaluating the complement inhibitory activity of Cp40, a potent analog of the peptidic C3 inhibitor compstatin.
- The binding of human xenoantibodies to iPECs led to serum dilution-dependent cell death.
- Pretreatment of the human serum with Cp40 almost completely inhibited the deposition of C3 fragments and C5b-9 on the cells, resulting in a dose-dependent inhibition of CDC against the iPECs.
- Using the same method to compare the effects of Cp40 on complement activation in humans, rhesus and cynomolgus monkeys, this study found that the inhibitory patterns were similar overall.
- Conclusion: In vitro xenoantibody-mediated CDC assay may have considerable potential for future clinical use.