VSIG4 Recombinant Monoclonal Antibody
Description
VSIG4 Biology and Antibody Targeting
VSIG4 is expressed predominantly on tissue-resident macrophages and TAMs, where it binds complement fragments (C3b/iC3b) to regulate immune responses . In cancer, elevated VSIG4 expression correlates with poor prognosis and immune evasion . Recombinant monoclonal antibodies block VSIG4-mediated suppression, enabling TAM repolarization and T-cell activation.
Key Features of VSIG4 Antibodies:
Mechanism of Action
Anti-VSIG4 antibodies disrupt TAM-mediated immune suppression through:
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TAM Repolarization: Induces M1-like macrophages by upregulating pro-inflammatory cytokines (e.g., TNF-α, IL-6) and chemokines (CXCL9/10, CCL4) .
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T-Cell Activation: Enhances CD8+ T-cell infiltration and activation in tumors, synergizing with anti-PD-1 therapy .
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Complement Pathway Modulation: Blocks VSIG4’s interaction with Siglec-7, preventing immunosuppressive signaling .
Example Data:
In ex vivo patient-derived tumor models (e.g., NSCLC, glioma), anti-VSIG4 treatment increased:
In Vitro Studies
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M2c Macrophage Repolarization: Human monocyte-derived M2c macrophages treated with anti-VSIG4 upregulated IL-12p40, IL-6, and IL-23, indicating M1 polarization .
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T-Cell Co-Culture Assays: Anti-VSIG4 + SEB-activated autologous T cells increased IFN-γ and IL-2 production, confirming T-cell priming .
In Vivo Syngeneic Models
Recombinant Production
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Phage Display: Libraries generated from immunized mice were screened for high-affinity Fab fragments (e.g., 12A12) .
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Chimeric Engineering: Murine variable regions fused to human IgG4 (S228P) for reduced immunogenicity (e.g., 12A12c) .
Functional Specificity
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Isoform Binding: Antibodies like 12A12c recognize both long and short VSIG4 isoforms, critical for targeting tumor-specific splicing variants .
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Glycosylation Independence: Ms x hVSIG4 528912.11 binds VSIG4 protein directly, avoiding off-target effects on glycosylated molecules (e.g., CD56/NCAM) .
Clinical Potential and Challenges
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Target Tumor Types: High VSIG4-expressing cancers (e.g., glioblastoma, NSCLC, pancreatic adenocarcinoma) are prioritized .
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Synergy with Immunotherapy: Combinations with anti-PD-1/PD-L1 may overcome resistance in “cold” tumors dominated by TAMs .
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Biomarker Validation: VSIG4 expression levels in bulk RNA-seq (TCGA) and scRNA-seq (NSCLC) highlight its tumor microenvironment specificity .
Product Specs
Constituents: 50% Glycerol, 0.01M PBS, pH 7.4
This VSIG4 monoclonal antibody is produced using recombinant human VSIG4 protein as the immunogen. The antibody's DNA sequence was obtained by sequencing the cDNA, followed by cloning into a plasmid vector. The plasmid vector containing the VSIG4 monoclonal antibody gene is then transfected into a suitable host cell. The VSIG4 recombinant monoclonal antibody undergoes affinity-chromatography purification and exhibits species specificity, reacting only with human targets. Its specificity has been validated through ELISA testing, demonstrating binding to the recombinant human VSIG4 protein (CSB-MP896869HU) with an EC50 of 51.14-68.73 ng/mL.
The VSIG4 protein plays a critical role in regulating immune responses by interacting with immune cells such as T cells and macrophages. It acts as both a co-stimulatory molecule, enhancing T cell activation, and an inhibitory molecule, suppressing macrophage function. Studies have shown that VSIG4 is involved in regulating autoimmune responses, tumor immunity, and infectious diseases. Additionally, it participates in the clearance of apoptotic cells and the maintenance of tissue homeostasis.
Target Background
- Elevated soluble VSIG4 levels are associated with the progression and recurrence of ovarian cancer. This suggests that soluble VSIG4 could be a potential biomarker for predicting tumor prognosis. PMID: 28498255
- VSIG4 signaling plays a crucial role in preventing the uncontrolled growth of intracellular bacteria within macrophages, providing an anti-immune evasion mechanism. PMID: 27440002
- The upregulation of VSIG4 by LMP1 is regulated at the transcriptional level through the NF-kB signaling pathway. PMID: 28859984
- VSIG4 expression is significantly increased in human masticatory mucosa during wound healing. PMID: 28005267
- Research indicates that let-7g-5p inhibits epithelial-mesenchymal transition (EMT), correlating with a reduction in glioma stem cell (GSC) phenotypes by targeting VSIG4 in glioblastoma. PMID: 27634309
- Evidence suggests that protein kinase calpha (PKCalpha) plays a role in downregulating complement receptor Ig (CRIg, encoded by V-set and Ig domain-containing protein 4 VSIG4) expression. PMID: 25687755
- The complement receptor of the immunoglobulin superfamily-L-factor H protects glomerular mesangial cells from complement-mediated injury and proliferative lesions. PMID: 25114177
- Research has identified VSIG4 as a potential diagnostic marker for severe preeclampsia, suggesting that its determination could enhance the prognostic assessment of this condition. PMID: 24349325
- Data indicate a significant infiltration of V-set and Ig domain-containing 4 VSIG4(+) cells throughout non-small-cell lung cancer samples. PMID: 24862966
- Studies have shown that a complement receptor of the Ig superfamily (CRIg, also known as Z39Ig), a receptor for complement fragments (C3b and iC3b), is expressed on a subset of intestinal macrophages in both murine and human large intestine. PMID: 21768202
- Research findings indicate that T cells can counteract T cell hyporesponsiveness by reducing inhibitory Z39Ig signals from macrophages, thereby maintaining their antiviral function in chronic hepatitis B. PMID: 20399148
- hVSIG4 recombinant adenovirus-transfected DCs suppress T cell proliferation, cytokine production, and activation marker expression. PMID: 19914289
- Research has identified and characterized a Complement Receptor of the Immunoglobulin superfamily, CRIg, which binds complement fragments C3b and iC3b. PMID: 16530040
- These findings suggest that the macrophage Z39Ig is involved in the pathogenesis of inflammatory diseases by inducing chemokine production, which promotes the migration of inflammatory cells into the lesion area, and MMP-9 induction. PMID: 16882875
- The specific expression of VSIG4 on resting macrophages suggests that it might play a crucial role in maintaining T cell unresponsiveness in healthy tissues. PMID: 17016562
- CRIg is not only a phagocytic receptor but also a potent inhibitor of the alternative pathway convertases. PMID: 17051150
