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首页> 美国政府科技报告 >Does Combination Immunotherapy With Human Monoclonal Antibodies Against HER2 and CXCR4 Augment Breast Cancer Killing in Vitro and Vivo
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Does Combination Immunotherapy With Human Monoclonal Antibodies Against HER2 and CXCR4 Augment Breast Cancer Killing in Vitro and Vivo

机译：联合免疫疗法与人单克隆抗体抗HER2和CXCR4增强乳腺癌体外和体内杀伤

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The chemokine receptor CXCR4 and its ligand CXCL12 (SDF1 ) have been proposed to regulate the directional migration and invasion of breast cancer cells to sites of metastasizes. The CXCR4 molecule could be a potential target to control breast cancer. Human epidermal growth factor receptor-2 (HER2) overexpression contributes to tumor progression and metastasis. A humanized monoclonal antibody Herceptin (Trastuzumab) is currently in clinical use. Thus, both of CXCR4 and HER2 play important roles in breast cancer progress, the linkage between CXCR4 and HER2 has also been reported. HER2 upregulates the expression of CXCR4, which is required for HER2-mediated lung invasion and metastasis. Therefore, we aimed to assess the anti-tumor effects of combinational immunotherapy by targeting both CXCR4 and HER2 in vitro and in a nude mice breast cancer model. The result from this study should provide pre- clinical data that may ultimately aid in testing the hypothesis that additive or synergistic effects of combinational treatment with anti-CXCR4 and anti-HER2 human Mabs may lead to an additive or synergistic effect in human clinical trials of breast cancer. We have produced enough antibodies for the entire study, and established the necessary cell lines for both in vitro and in vivo studies. We have evaluated the effects of CXCR4 Mabs in combination of Herceptin or alone on inhibition of chemotaxis, invasion and proliferation on breast cancer cells. The results and experience we have obtained through these studies will lead us to answer the question we have proposed and guide us to perform the in vivo studies which will be started in the next year.

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