Conversion of Non-Toxic Prodrugs to Active, Anti-Neoplastic Drugs Selectively in Breast Cancer Metastases

摘要

We have evaluated the ability of tumor-seeking carrier-cells labeled with Thyl antibodies directly conjugated with AP. While many carriers were found in the tumor tissue at 12, 24 and 48 hours after injection, very little enzymatic activity was found in the malignant tissues. We conclude that although well retained on carrier-cell surfaces in vitro, even a directly conjugated antibody is 'stripped' from the cells in vivo. We have found evidence that this happens during the cell passage through the liver. We speculate that this might be due to macrophages, which are know to strip red blood cells for surface- attached immune complexes. Since this stripping is mediated via Ec- receptors on the macrophages, it is possible that F(ab')2-fragments will not be stripped from the carrier- cell surface. We are now in the process of producing Ap-labeled F(ab')2-fragments of the Thyl.2 antibody. In addition, a biotin-based method for attaching AP to the carrier-cells is being tested. We believe that we, using carrier-cell labeled by one or both of these methods, will be able to deliver prodrug-activating enzymes selectively to breast cancer metastases.