IAN11 Antibody
Description
What Are IL-11 Antibodies?
IL-11 antibodies are monoclonal antibodies (mAbs) designed to inhibit the activity of interleukin-11 (IL-11), a cytokine belonging to the IL-6 family. IL-11 is implicated in fibrosis, inflammation, and cellular senescence . These antibodies bind directly to IL-11 or its receptor (IL-11Rα), blocking downstream signaling pathways such as ERK, STAT3, and SMAD .
Key Features of IL-11 Antibodies:
| Property | Description |
|---|---|
| Target | IL-11 or IL-11 receptor α-subunit (IL-11Rα) |
| Format | Humanized or fully human IgG1/IgG4 |
| Mechanism | Neutralizes free IL-11 or prevents IL-11/IL-11Rα complex formation |
| Therapeutic Areas | Fibrotic diseases (pulmonary, renal, hepatic), aging-related disorders, cancer-associated fibrosis |
Mechanism of Action
IL-11 antibodies function through two primary strategies:
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Direct IL-11 Neutralization: Antibodies like X203 bind to IL-11, preventing its interaction with IL-11Rα .
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Receptor Blockade: Antibodies like LASN01 target IL-11Rα, inhibiting signal transduction through the gp130 co-receptor .
Key Pathways Affected:
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Fibrosis: IL-11 drives epithelial-to-mesenchymal transition (EMT) and collagen deposition via ERK and SMAD activation .
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Inflammation: IL-11 amplifies pro-inflammatory cytokine production (e.g., IL-8, MCP-1) .
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Aging: IL-11 upregulation correlates with age-related metabolic dysfunction and frailty; inhibition extends lifespan in preclinical models .
Table 1: Efficacy of IL-11 Antibodies in Disease Models
Table 2: Anti-IL-11 Antibodies in Clinical Trials
Recent Updates:
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LASN01 demonstrated inhibition of procollagen and TIMP-1 in ex vivo human IPF lung tissue .
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Phase 1 trials focus on safety, pharmacokinetics, and immunogenicity in healthy volunteers .
Comparative Analysis of IL-11 Antibodies
| Feature | X203 (IL-11 mAb) | LASN01 (IL-11Rα mAb) |
|---|---|---|
| Target | IL-11 cytokine | IL-11 receptor α-subunit |
| Half-Life | ~11 days (preclinical) | Pending clinical data |
| Key Advantage | Broad fibrosis mitigation | Potent TGF-β pathway synergy |
| Stage | Preclinical | Phase 1 |
Challenges and Future Directions
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Timing of Intervention: Anti-IL-11 therapies show maximal efficacy in early disease stages, with limited reversal of established fibrosis .
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Biomarker Development: Ultra-sensitive assays (e.g., Simoa SP-X) detect IL-11 at 0.006 pg/mL, enabling precise patient stratification .
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Combination Therapies: Potential synergy with anti-TGF-β or antifibrotics (e.g., nintedanib) is under exploration .
Product Specs
Composition: 50% Glycerol, 0.01M Phosphate Buffered Saline (PBS), pH 7.4
Q&A
FAQs for Researchers Investigating IL-11 Antibodies
(Note: "IAN11" is not referenced in available literature; responses focus on IL-11 and IPO11 antibodies based on search results.)
How do I validate IL-11 antibody specificity in preclinical models?
Methodological Answer:
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Knockout Validation: Use IL-11 gene-deleted mice (e.g., Il11−/− strains) to confirm antibody specificity. Loss of signal in Western blot (WB) or immunohistochemistry (IHC) in knockout tissues confirms target engagement .
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Neutralization Assays: Test monoclonal antibodies (e.g., X203, X209) in HEK cell lines overexpressing IL-11/IL-11RA. Measure STAT3/ERK phosphorylation inhibition via flow cytometry or phospho-specific ELISAs .
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Cross-Reactivity: Quantify binding affinity using Biacore T200 or Octet systems. For example, X203 shows 2.38 nM (mouse) and 4.14 nM (human) IL-11 binding .
What experimental models are optimal for studying IL-11-mediated fibrosis?
Methodological Answer:
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In Vivo Models:
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Ex Vivo Systems:
How do I distinguish IL-11’s pro-fibrotic vs. anti-inflammatory roles?
Methodological Answer:
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Temporal Analysis: Measure IL-11 expression kinetics using qPCR/WB during early (inflammatory) vs. late (fibrotic) disease phases.
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Cell-Specific Targeting: Use Cre-lox systems (e.g., Col1a2-CreERT2) to delete IL-11 in fibroblasts vs. macrophages .
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Pathway Inhibition: Compare outcomes of IL-11 neutralization (X203) vs. IL-11RA blockade (X209) to isolate receptor-specific effects .
How to resolve contradictions in IL-11’s role across tissues (e.g., protective in liver vs. pathogenic in lung)?
Methodological Answer:
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Tissue-Specific Transcriptomics: Perform single-cell RNA sequencing on IL-11-treated liver vs. lung tissues to identify divergent signaling nodes (e.g., STAT3 vs. SMAD1/5) .
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Paracrine vs. Autocrine Signaling: Use transwell co-cultures of epithelial cells and fibroblasts to map IL-11 secretion dynamics .
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Data Table:
| Tissue | Primary IL-11 Source | Dominant Pathway | Outcome | Citation |
|---|---|---|---|---|
| Liver | Hepatocytes | ERK/MEK | Regeneration | |
| Lung | Fibroblasts | STAT3/JAK2 | Fibrosis |
What strategies improve antibody penetration in fibrotic tissues?
Methodological Answer:
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Antibody Engineering: Use RFdiffusion AI models to design single-chain variable fragments (scFvs) with reduced hydrodynamic radius .
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Carrier Systems: Conjugate IL-11 antibodies to hyaluronidase-PEG nanoparticles for enhanced diffusion in collagen-dense matrices .
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Dosing Optimization: Administer X203 at 10 mg/kg twice weekly in aged mice, correlating with reduced pSMAD2/3 levels in fibrotic loci .
How to address variability in IL-11 antibody performance across assays?
Methodological Answer:
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Assay Harmonization:
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Validation Panel: Include ≥3 orthogonal assays (e.g., SPR for affinity, IF for localization, functional neutralization) .
Can AI-designed antibodies (e.g., RFdiffusion) accelerate IL-11 inhibitor development?
Methodological Answer:
Key Data from Preclinical Studies
Table 1: Efficacy of IL-11 Neutralization in Aging Mice
| Parameter | Wild-Type | Il11−/− | X203-Treated |
|---|---|---|---|
| Median Lifespan | 120 weeks | 155 weeks | 148 weeks |
| Muscle Strength | 0.5 N/cm² | 1.2 N/cm² | 1.1 N/cm² |
| Serum IL-6 | 120 pg/mL | 40 pg/mL | 55 pg/mL |
Table 2: Antibody Characterization
| Antibody | Target | Affinity (nM) | Validated Applications |
|---|---|---|---|
| X203 | IL-11 | 2.38 (mouse) | WB, IF, in vivo neutralization |
| X209 | IL-11RA | 4.14 (human) | IHC, flow cytometry |
| HPA065346 | IPO11 | N/A | WB, ICC-IF |
