Radioimmunotherapy of Metastatic Breast Cancer Using Radiolabeled Tumor Specific Antibodies

摘要

Over the last four years we conducted and published a radioimaging trial using In-i ii Mx-DTPA huBrE-3 in patients with metastatic breast cancer. The results suggest that it is possible to administer therapeutic doses of Y-90 NX-DTPA huBrE-3 to patients. We are currently enrolling patients onto therapeutic trials of dose fractionated Y-90 NX-DTPA huBrE-3 to patients with metastatic breast cancer. We have also performed numerous preclinical experiments in the nude mouse human tumor xemograft model. We have demonstrated significant anti-tumor efficacy of combination continuous infusion topotecan and Y-90 MX-DTPA BrE-3. After tumors were allowed to grow for 21 days, the combination of 2OOu%i of 9OYttrium and 1 mg/m2 for 14 days via Alzet pump demonstrated complete tumor regression in 10 of 13 mice. As demonstrated in subsequent experiments, tumor response was specific to the BrE-3 antibody. This effect persisted with dose fractionation of antibody. In vivo studies demonstrated an increase in apoptosis and a decrease cell proliferation rate which was additive in the presence of topotecan and Y-90 MX-DTPA BrE-3. In our final year we continued these experiments using gemcitabine in a human pancreative cell xenograft nude mouse model and demonstrated significant activity of combination Y-90 MX-DTPA BrE-3 and gemcitabine.