Grants and Contracts Details
In response to the Kentucky Lung Cancer Research initiative, we propose to produce a second-generation antibody targeting the HER-2 gene product on lung tumors expressing the HER-2/neu growth factor receptor. This proposal is based on previous work in which we used an autophilic peptide to convert monovalent antibodies into polyvalent molecules with enhanced binding and biological properties. CUITentlythere are several clinical trials ongoing with Herceptin in lung cancer patients. Because Herceptin provides a unique therapy window for lung cancer patients, improving the therapeutic lefficacy could generate significant benefits with regard to reducing the therapeutic dose, increasing jthe synergy with chemotherapy and extending the therapeutic window to tumors with lower !expression of the HER-2/neu receptor. This goal will be achieved by increasing the avidity of !Trastuzumab through the use of an autophilic peptide. In the specific aims, we will generate an autophilic Trastuzumab antibody against HER-2 gene product and demonstrate improved tumor targeting, test for enhanced ADCC and CDC, cell cycle inhibition and apoptosis, and inhibition of cell growth. These pilot studies will set the stage to evaluate the autophilic modification of . Herceptin in future clincial studies.
|Effective start/end date||8/1/02 → 8/30/05|
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