Targeting Breast Cancer With Anti HER2/neu Diabodies
Annual rept. 22 Jun 2000-21 Jun 2001
FOX CHASE CANCER CENTER PHILADELPHIA PA
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The objective of this proposal is to develop new therapeutic reagents for breast cancer. It is our hypothesis that improved diabody-based molecules with affinity for HER2neu can be engineered and will prove to be effective vehicles for the radioimmunotherapy RAIT of breast cancer. The first Technical Objective T.O. focuses on the optimization of the production of the selected diabody and the identification of the optimal radionuclide and labeling strategy for diabody-based RAIT. This T.O. also involves an investigation into the impact on diabody targeting and RAIT of a variety of factors likely to be encountered in a clinical setting. These include the degree of antigen density, the route i.v. bolus or continuous infusion and frequency of administration, the presence of disseminated disease, and the effect of antigen expression on normal tissues. Completion of these experiments will set the stage for proceeding to the clinical evaluation of diabody-based targeting of breast cancer in our second Technical Objective. The clinical component of this proposal to be initiated in year 3 will entail a Phase I radioimmunoimaging and radioimmunoguided surgery trial designed to elicit information on the dosimetry, specificity and tumor penetration properties of radiolabeled C6.5 diabody, and will assess the RAIT potential of this molecule.
- Anatomy and Physiology