An epitope-specific novel anti-EMMPRIN polyclonal antibody inhibits tumor progression

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Extracellular matrix metalloproteinase inducer (EMMPRIN/CD147) is crucial for tumor cell-macrophage interactions, inducing matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF).
• The specific EMMPRIN epitope responsible for MMP induction is debated, and its role in VEGF induction remains unclear.

Purpose of the Study:

• To develop and characterize a novel anti-EMMPRIN antibody targeting a specific epitope.
• To investigate the antibody's efficacy in inhibiting tumor progression, angiogenesis, proliferation, and metastasis.
• To elucidate the antibody's impact on the tumor microenvironment and macrophage-mediated anti-tumor immunity.

Main Methods:

• Generation of a novel anti-EMMPRIN antibody targeting a specific epitope.
• In vitro co-culture systems to assess MMP-9 and VEGF production.
• In vivo studies using RENCA, CT26, and 4T1 tumor models to evaluate tumor progression, angiogenesis (CD31 staining), proliferation (Ki-67 staining), and apoptosis (TUNEL assay).
• Analysis of macrophage infiltration and polarization within the tumor microenvironment.
• Assessment of antibody-dependent cell-mediated cytotoxicity (ADCC) of macrophages.

Main Results:

• The novel antibody successfully inhibited MMP-9 and VEGF production in vitro, exhibiting a U-shaped dose response.
• Significant inhibition of tumor progression, reduced tumor size, and decreased metastasis were observed in vivo.
• The antibody suppressed angiogenesis and tumor cell proliferation while enhancing tumor cell apoptosis.
• Macrophage recruitment into tumors increased, shifting the microenvironment from immunosuppressive to less suppressive.
• Enhanced macrophage-mediated ADCC against tumor cells was observed.

Conclusions:

• The developed anti-EMMPRIN antibody effectively targets a critical epitope, inhibiting both MMPs and VEGF, thereby suppressing tumor growth and metastasis.
• This antibody demonstrates potential as a therapeutic agent by not only directly impacting tumor cells but also by reprogramming the tumor microenvironment to enhance anti-tumor immunity.
• EMMPRIN represents a promising therapeutic target for various cancers.