Targeting Breast Cancer with Anti HER2/neu Diabodies

Abstract : The objective of this proposal is to develop new therapeutic reagents for breast cancer using diabody-based molecules with affinity for HER2/neu for the radioimmunotherapy (RAIT) of breast cancer. The first Technical Objective (T.O.) has focused 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 has involved an investigation into the impact on diabody targeting 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 has set the stage for proceeding to the clinical evaluation of diabody-based targeting of breast cancer in our second Technical Objective. Current experiments demonstrate the feasibility and efficacy of alpha particle based radioimmunotherapy wherein the radionuclide is conjugated to a chelated diabody molecule. The clinical component of this proposal will entail a Phase I radioimmunoimaging and radioimmunoguided surgery trial 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.