IL18BP Monoclonal Antibody
Description
Introduction to IL18BP Monoclonal Antibody
IL18BP (Interleukin-18 Binding Protein) is a soluble decoy receptor that binds to IL-18 with high affinity, neutralizing its proinflammatory and immune-stimulatory effects . Monoclonal antibodies targeting IL18BP are engineered to disrupt this interaction, releasing IL-18 to enhance immune responses. These antibodies are under investigation for therapeutic applications in oncology and autoimmune diseases, where IL-18 activity is suppressed due to elevated IL18BP levels .
Mechanism of Action
IL18BP monoclonal antibodies function by:
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Blocking IL-18/IL18BP complex formation: Prevents IL18BP from binding to IL-18, enabling IL-18 to activate its cognate receptors (IL-18Rα/β) .
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Disrupting pre-formed complexes: High-affinity antibodies (e.g., clone 445) release IL-18 bound to IL18BP, restoring its biological activity .
Development and Antibody Clones
Multiple IL18BP-specific monoclonal antibodies have been developed for research and therapeutic use:
Table 1: Key IL18BP Monoclonal Antibodies
Key Findings:
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Clone 445: Demonstrates potent IL-18BP antagonism, exacerbating CpG-induced macrophage activation syndrome (MAS) in mice .
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COM503: Fully human antibody with tumor-localized immune modulation, sparing systemic tissues .
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Clone 441: Non-neutralizing antibody used as a negative control in functional assays .
Oncology
IL18BP antibodies enhance anti-tumor immunity by:
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Releasing endogenous IL-18: Restores immune cell activation (NK, T cells) in the tumor microenvironment (TME) .
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Synergizing with checkpoint inhibitors: Combining anti-IL18BP with anti-PD-1 improves tumor control in murine models (e.g., MC38OVA, E0771) .
Example Data:
| Model | Treatment | Outcome |
|---|---|---|
| MC38OVA | Anti-IL18BP + anti-PD-1 | Complete responses in >50% mice |
| B16/Db-hmgp100 | Anti-IL18BP monotherapy | Significant tumor growth inhibition |
Inflammatory and Autoimmune Diseases
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CpG-induced MAS: IL18BP KO mice show exaggerated IL-18 signaling and MAS severity, highlighting its regulatory role .
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Erythropoiesis: IL18BP-producing erythroid precursors attenuate IL-18-mediated anemia in murine MAS models .
Challenges and Considerations
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Specificity vs. Cross-Reactivity: Some antibodies (e.g., 441) fail to disrupt IL-18/IL18BP complexes, necessitating rigorous validation .
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Safety Risks: Neutralizing IL18BP may lead to systemic inflammation, as seen in IL18BP KO mice .
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Therapeutic Window: Tumor-localized immune modulation is critical to minimize off-tumor toxicity .
Future Directions
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Clinical Translation: Humanized antibodies (e.g., COM503) are advancing toward clinical trials for solid tumors .
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Biomarker Development: Identifying IL18BP/IL-18 ratios as predictors of therapeutic response .
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Combination Strategies: Exploring synergy with IL-18 agonists or other cytokine therapies .
