The ultimate goal of this work is to produce clinically useful, commercially viable, therapy agent for breast cancer. Radioimmunotherapy has shown clinical efficacy against radiosensitive lymphomas in recent years, and is considered a potentially attractive modality for treating metastatic breast cancer. The therapy agent will be based on a humanized monoclonal antibody (hMAb) hRS7, which targets a breast cancer antigen and which would minimize patient immune response to MAb in eventual clinical application. Phase II work will involve humanization of RS7, process optimizations for clinical-scale radioiodinations, and extensive experimentations to demonstrate preclinical utility of the proposed agent in subcutaneous and systemic animal models of breast cancer. The internalizing hRS7 will be radiolabeled with a residualizing form of I-131 radionuclide, developed in Phase I, so as to increase the retention of the nuclide in the tumor and thereby enhance therapeutic efficacy. The goals are to achieve clinical- scale radiolabelings of hRS7 with >90% efficiency and about 10 mCi/mg of specific activity, and establish significant therapeutic advantage of the optimized product compared to conventionally radioiodinated hRS7, irrelevant hMAb and untreated control. Promising radiochemistry and preclinical results will form the basis for clinical studies in Phase III.
Radioimmunotherapy (RAIT) is a promising treatment modality, worthy of exploration as adjuvant systemic therapy of metastatic breast cancer in patients with poor prognosis. To realize the full potential of RAIT in this regard, commercially viable optimum delivery agents, such as improved radioiodinated humanized antibodies, must be used. The proposed Phase II research addresses these important issues.
