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Using an in vitro xenoantibody-mediated complement-dependent cytotoxicity model to evaluate the complement inhibitory activity of the peptidic C3 inhibitor Cp40

November 21, 2015

Highlights:
  • 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.
Author and source information

Authors:Wang J, Wang L, Xiang Y, Ricklin D, Lambris JD, Chen G.

Reference: Clin Immunol. 2015 Nov 6;162:37-44. doi: 10.1016/j.clim.2015.11.002. [Epub ahead of print]
Source: www.ncbi.nlm.nih.gov

 

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