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Published on: September 12, 2019
Antibody mediated therapy targeting CD47 inhibits tumor progression of hepatocellular carcinoma
Zhenyu Xiao1, Haniee Chung1, Babak Banan1
1Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA.
Abstract:
Human hepatocellular carcinoma (HCC) has a high rate of tumor recurrence and metastasis, resulting in shortened survival times. The efficacy of current systemic therapies for HCC is limited. In this study, we used xenograft tumor models to investigate the use of antibodies that block CD47 and inhibit HCC tumor growth. Immunostaining of tumor tissue and HCC cell lines demonstrated CD47 over-expression in HCC as compared to normal hepatocytes. Macrophage phagocytosis of HCC cells was increased after treatment with CD47 antibodies (CD47mAbs) that block CD47 binding to SIRPα. Further, CD47 blockade inhibited tumor growth in both heterotopic and orthotopic models of HCC, and promoted the migration of macrophages into the tumor mass. Our results demonstrate that targeting CD47 by specific antibodies has potential immunotherapeutic efficacy in human HCC.
Insights
Targeting CD47 with antibodies shows promise for treating human hepatocellular carcinoma (HCC). This approach enhances immune cell activity against cancer cells, inhibiting tumor growth and metastasis in preclinical models.
Area of Science:
- Immunology
- Oncology
- Hepatocellular Carcinoma Research
Background:
- Hepatocellular carcinoma (HCC) presents significant challenges due to high recurrence and metastasis rates.
- Current systemic therapies for HCC demonstrate limited efficacy, necessitating novel treatment strategies.
Purpose of the Study:
- To investigate the potential of CD47-blocking antibodies as an immunotherapeutic approach for human HCC.
- To evaluate the impact of CD47 blockade on HCC tumor growth and immune cell activity in preclinical models.
Main Methods:
- Utilized xenograft tumor models to assess the efficacy of CD47 blockade.
- Performed immunostaining to confirm CD47 overexpression in HCC tissues and cell lines.
- Administered CD47-blocking antibodies (CD47mAbs) and analyzed effects on macrophage phagocytosis, tumor growth, and immune cell infiltration.
Main Results:
- Confirmed significant CD47 overexpression in HCC compared to normal hepatocytes.
- Demonstrated increased macrophage phagocytosis of HCC cells upon CD47 antibody treatment.
- Observed inhibition of tumor growth in both heterotopic and orthotopic HCC models with CD47 blockade.
- Noted enhanced migration of macrophages into the tumor microenvironment following CD47 targeting.
Conclusions:
- Targeting CD47 with specific antibodies exhibits potential as an immunotherapeutic strategy for human HCC.
- CD47 blockade can enhance anti-tumor immunity by promoting macrophage-mediated phagocytosis and infiltration.
- This approach offers a promising avenue for improving outcomes in patients with hepatocellular carcinoma.
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