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Safety profile after prolonged C3 inhibition
Edimara S Reis1, Nadja Berger1, Xin Wang1
1Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Clinical Immunology (Orlando, Fla.)
|September 16, 2018
Summary
Systemic inhibition of complement component 3 (C3) using compstatin in adult non-human primates did not impair immune function or increase infection susceptibility. This suggests C3 inhibition is safe for therapeutic use in adults.
Area of Science:
- Immunology
- Biochemistry
- Pharmacology
Background:
- Complement component 3 (C3) is crucial for immune responses, including phagocytosis and microbial clearance.
- C3 deficiency in humans is linked to bacterial infections, particularly in early life.
- Therapeutic C3 inhibition is approached cautiously due to its central role in immunity.
Purpose of the Study:
- To investigate the safety and immunological effects of prolonged systemic C3 inhibition.
- To assess the impact of the C3 inhibitor compstatin (Cp40) on healthy adult non-human primates.
- To evaluate potential risks of infection or immune compromise associated with C3 inhibition.
Main Methods:
- Cynomolgus monkeys received subcutaneous Cp40 for varying durations (1 week to 3 months).
- Plasma C3 and Cp40 levels were monitored to confirm C3 inhibition.
- Hematological, biochemical, immunological parameters, and wound healing were assessed.
- A biodistribution study was conducted in rhesus monkeys.
Main Results:
- Complete systemic C3 inhibition was achieved and maintained.
- No significant differences were observed in hematological, biochemical, or immunological parameters between Cp40-treated and control groups.
- Cp40 treatment did not lead to infection in skin wounds and showed a trend toward accelerated healing.
- Cp40 distribution correlated with C3 presence in blood-rich organs.
Conclusions:
- Systemic C3 inhibition with Cp40 is well-tolerated in adult non-human primates.
- Prolonged C3 inhibition does not appear to compromise the immune system or increase infection risk in healthy adults.
- These findings support the potential therapeutic use of C3 inhibitors in adult populations.
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