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Use of nano-scale phage display selection for the generation of human monoclonal antibodies against breast cancer
Charlotte
G. Jakobsen, Nicolaj Rasmussen, Henrik J.
Ditzel The current goal of cancer drug discovery and development is to identify agents that are effective cancer therapeutics and yet have minimal systemic side effects. Therefore targeted drug design directed towards molecular pathways that underlie the malignant phenotype has been initiated. These therapies are targeted against specific tumor cell receptors or signaling events that are critical to tumor progression while reducing toxicity to normal cells. One way to direct activity against therapeutic targets is to use monoclonal antibodies directed to growth factor receptors, tumor-associated antigens or antigens differentially expressed on cancer cells. We are using very large antibody phage display libraries to isolate and characterize human monoclonal antibody fragment that specifically recognize breast cancer-associated cell surface proteins and which can be used as nanodevices for diagnosis and/or therapy of cancer patients. Our focus is on isolation of antibodies specific for surface proteins associated with high metastatic potential and we have optimized nano-scale selection strategies for antibodies recognizing cell surface molecules central for relevant biological functions, such as cancer cell proliferation, adhesion, migration and invasion. The long-term goal is to conjugate the cloned human antibody fragments and use them as nanodevices for in vivo diagnosis and/or therapy of cancer patients.
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Presented at the
International Congress of Nanotechnology, November 7-10, 2004
San Francisco, USA
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