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The effect of antibody against vascular endothelial growth factor on tumor growth and metastasis
Abstract:
Vascular endothelial growth factor (VEGF), a very important in the process of tumor angiogenesis, was chosen as a target in a study to determine whether manipulation of angiogenesis with antibody against VEGF may interrupt tumor growth and metastasis. Anti-VEGF antibody was obtained from immunized rabbits, purified on an affinity column, and identified as neutralized antibody by Mile's assay. IVTA2MA891, a murine spontaneous breast cancer with a high rate of metastasis in lung in TA2 x 615 F1 mice, was chosen as an animal model in this study, because of the high expression of VEGF in the primary tumor as well as in the lung metastatic tumor. The anti-VEGF antibody could inhibit growth of S180 sarcoma in a dose-dependent manner, and the inhibition rate could reach 41.0% with a dose of 200 microg mouse(-1) day(-1). Anti-VEGF antibody could inhibit tumor growth by 76.2% in nude mice bearing human gastric cancer (MGC 803). When anti-VEGF antibody was combined with 131I-3H11, a murine monoclonal antibody conjugated with 131I, only one of five nude mice developed tumor and 84.0% more inhibition of tumor growth was obtained in comparison with treatment by 131I-3H11 alone. The growth of the primary tumor was inhibited by 44.0% and the number and size of the metastatic foci in the lungs were reduced by 73.0% and 83.7% respectively in the animal model, with a high rate of metastasis in lung. The anti-VEGF antibody may be potentially useful for clinical treatment of cancer and metastasis.
Insights
This study shows that antibodies targeting vascular endothelial growth factor (VEGF) can significantly inhibit tumor growth and metastasis. These findings suggest anti-VEGF antibodies hold promise for clinical cancer treatment.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Vascular endothelial growth factor (VEGF) is crucial for tumor angiogenesis.
- Targeting VEGF is a strategy to inhibit tumor growth and metastasis.
Purpose of the Study:
- To investigate the efficacy of anti-VEGF antibodies in inhibiting tumor growth and metastasis.
- To evaluate anti-VEGF antibody therapy in preclinical cancer models.
Main Methods:
- Production and purification of anti-VEGF antibody.
- In vivo studies using murine breast cancer and human gastric cancer models.
- Combination therapy with anti-VEGF antibody and radiolabeled antibody (131I-3H11).
Main Results:
- Anti-VEGF antibody demonstrated dose-dependent inhibition of S180 sarcoma growth (up to 41.0%).
- Significant inhibition of human gastric cancer growth (76.2%) in nude mice.
- Combination therapy achieved 84.0% greater tumor growth inhibition compared to radiolabeled antibody alone.
- Reduced primary tumor growth (44.0%) and lung metastasis (73.0% reduction in foci number, 83.7% reduction in size) in a metastatic breast cancer model.
Conclusions:
- Anti-VEGF antibody therapy effectively inhibits tumor growth and metastasis in preclinical models.
- Combination therapy enhances anti-tumor efficacy.
- Anti-VEGF antibodies show potential for clinical application in cancer treatment.