ENHANCED TUMOR-LOCALIZATION OF MONOCLONAL-ANTIBODY BY TREATMENT WITH KININASE-II INHIBITOR AND ANGIOTENSIN-II

The effect of kininase II inhibitor, enalapril, on the delivery of mon oclonal antibody A7 to the targeted tumor was investigated using athym ic mice bearing human colon cancer, SW1116. Enalapril alone, which enh ances tumor vascular permeability through the kinin-generating cascade , did not increase the uptake of I-125-labeled A7 (I-125-A7) in SW1116 due to the systemic hypotension induced by its inhibitory effect on a ngiotensin converting enzyme. However, with combined angiotensin II (A T-II) and enalapril treatment, a 2-fold increase in the accumulation o f I-125-A7 was seen when compared to A7 alone. This marked increase wa s presumably due to increased tumor vascular permeability induced by e nalapril combined with the absence of hypotension due to the actions o f AT-II. This approach might be useful in radioimmunodetection and imm unotargeting chemotherapy using monoclonal antibody.