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In Vitro Methods for Comparing Target Binding and CDC Induction Between Therapeutic Antibodies: Applications in Biosimilarity Analysis
Published on: May 4, 2017
The Therapeutic Potential of Complement Inhibitors in Xenoreactive Human Complement-Dependent Cytotoxicity in Vitro
Krish Vasudev1, Maho Terashita1, David K C Cooper1
1Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA.
Xenotransplantation
|June 2, 2026
Summary
Pegcetacoplan, a C3/C3b inhibitor, effectively blocked xenograft complement activation in vitro. Other inhibitors showed limited efficacy, highlighting pegcetacoplan
Area of Science:
- Immunology
- Transplantation
- Pharmacology
Background:
- Complement activation is a key factor in xenograft rejection.
- The comparative effectiveness of different complement inhibitors is not well-established.
Purpose of the Study:
- To evaluate the efficacy of various pharmacological complement inhibitors against human complement activation.
- To compare the inhibitory effects of C1s, C1-esterase, C3/C3b, and C5 inhibitors on xenoreactive complement.
Main Methods:
- Peripheral blood mononuclear cells (PBMCs) from wild-type pigs were incubated with human serum.
- Dose-response assays were performed using C1s inhibitor (sutimlimab), C1-esterase inhibitor (berinert), C3/C3b inhibitor (pegcetacoplan), and C5 inhibitor (tesidolumab).
- Complement-dependent cytotoxicity (CDC) and complement deposition were quantified using flow cytometry.
Main Results:
- Pegcetacoplan (C3/C3b inhibitor) completely inhibited CDC and minimized complement deposition (C3b/iC3b, C5b-9).
- Sutimlimab (C1s inhibitor) provided partial CDC inhibition and reduced complement deposition.
- C1-esterase inhibitor showed limited CDC effect, while tesidolumab (C5 inhibitor) inhibited C5b-9 but not CDC or opsonization.
Conclusions:
- Pegcetacoplan demonstrated the most potent inhibition of xenoreactive human complement activation in this experimental model.
- The efficacy of the C5 inhibitor tesidolumab warrants further investigation, including comparison with other C5 inhibitors like eculizumab.
- Additional studies are needed to clarify the clinical applicability of these complement inhibitors in xenotransplantation.
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