Does Combination Immunotherapy with Human Monoclonal Antibodies Against HER2 and CXCR4 Augment Breast Cancer Killing in Vitro and in Vivo
Abstract
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 mouse breast cancer model. We have produced enough antibodies for the entire study, and established the CXCR4 expressing cell lines for both in vitro and in vivo studies. We have evaluated the effects of anti- CXCR4 Mabs in combination of Herceptin oralone on inhibition of chemotaxis, invasion and proliferation on breast cancer cells. We also tested the function of two anti-CXCR4 Mabs in animal model. To data, we have not been able to demonstrate anti-tumor activities of our anti-CXCR4 MAbs in vitro or in vivo which we believe are, at least in part, due to technical problems with our assays and low expression of CXCR4 on the tumor cells used for in vivo assays. We are continuing to address these issues so we can answer the questions we have proposed in the future.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2007
- Accession Number
- ADA474949
Entities
People
- Wayne A Marasco
Organizations
- Dana–Farber Cancer Institute