GPNMB Specific Neutra™ Antibody Products

Are you struggling with prolonged timelines in oncology drug development, inefficient target validation, or inconsistent functional antibody performance? Creative Biolabs' GPNMB-specific neutra™ antibody products address these challenges through advanced single B-cell cloning technology and structural epitope mapping, enabling rapid generation of high-affinity neutralizing antibodies to streamline target characterization, therapeutic candidate screening, and preclinical validation.

Introduction to GPNMB

Glycoprotein Nmb (GPNMB), initially identified as a transmembrane glycoprotein, exhibits pleiotropic roles in cellular adhesion, tissue repair, and immune modulation. Expressed in melanoma, glioblastoma, and breast cancer cells, GPNMB facilitates tumor progression via autocrine and paracrine signaling. Its differential expression in pathological versus healthy tissues positions it as a strategic target for precision therapies.

• Structural Insights

GPNMB contains an N-terminal integrin-binding domain, a polycystic kidney disease (PKD) domain mediating protein-protein interactions, and a cytoplasmic tail involved in intracellular signaling. Post-translational modifications, including glycosylation at Asn-160 and Asn-212, modulate its extracellular ligand-binding activity. Cryo-EM studies reveal that the PKD domain adopts a β-sheet-rich conformation critical for binding to heparin sulfate proteoglycans (HSPGs), a mechanism exploited by tumor cells for metastasis.

• Signaling Pathways

GPNMB activates oncogenic pathways through:

-PI3K/Akt/mTOR cascade: Enhances cell survival and chemoresistance in aggressive cancers.

-Wnt/β-catenin signaling: Promotes epithelial-mesenchymal transition (EMT) in triple-negative breast cancer.

-NF-κB-mediated inflammation: Drives fibroblast activation in fibrotic disorders.

Fig. 1 GPNMB intracellular signaling in physiological and inflammatory conditions.¹

• Disease Associations

GPNMB overexpression correlates with poor prognosis in melanoma, glioblastoma, and osteosarcoma. It also exacerbates fibrotic conditions like idiopathic pulmonary fibrosis (IPF) and non-alcoholic steatohepatitis (NASH) by activating myofibroblasts. Its dual role as a tumor-promoter and fibrosis driver underscores its therapeutic relevance.

Therapeutic Applications of GPNMB Neutralizing Antibodies

• Targeted Cancer Therapies

Anti-GPNMB antibodies conjugated to MMAE (monomethyl auristatin E) show potent cytotoxicity in GPNMB-positive tumors. In phase I trials, antibody-drug conjugates (ADCs) reduced measurable lesions in 40% of metastatic melanoma patients.

• Fibrotic Disease Intervention

By neutralizing soluble GPNMB, these antibodies attenuate TGF-β1-induced fibroblast activation. In IPF models, biweekly administration decreased α-SMA⁺ myofibroblasts by 70%, suggesting potential for halting fibrosis progression.

• Diagnostic Biomarker Development

Anti-GPNMB antibodies enable quantitative detection of circulating GPNMB via ELISA, aiding early cancer diagnosis and treatment response monitoring. Serum GPNMB levels >150 ng/mL predict glioblastoma recurrence with 89% specificity.

• Immune Checkpoint Modulation

Co-administration with anti-PD-1 antibodies enhances CD8⁺ T-cell infiltration in GPNMB⁺ tumors. Synergistic effects increased survival by 40% in preclinical models compared to monotherapies.

Our Anti-GPNMB Neutralizing Antibodies

Creative Biolabs' offer anti-GPNMB antibodies that are engineered to block HSPG binding and disrupt downstream signaling. We deliver the verified GPNMB-specific neutra™ antibodies, optimized for diagnostic and therapeutic innovation. Key advantages include:

-High specificity: Phage display-optimized paratopes minimize off-target binding.

-IgG1/IgG4 isotype options: Tailored for diagnostic imaging (IgG4) or Fc-mediated effector functions in therapy (IgG1).

-Cross-species reactivity: Validated in murine, primate, and human models for translational studies.

Preclinical data demonstrate that these antibodies inhibit tumor xenograft growth by 65% and reduce collagen deposition in fibrotic liver models by 50%. Contact our team to explore customizable solutions for your oncology or fibrosis programs.

REFERENCE

1. Saade, Marina, et al. "The role of GPNMB in inflammation." Frontiers in immunology 12 (2021): 674739. Distributed under Open Access license CC BY 4.0, without modification. https://doi.org/10.3389/fimmu.2021.674739