Grants and Contracts Details
Description
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.
Status | Finished |
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Effective start/end date | 8/1/02 → 8/30/05 |
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