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 monoclonal antibody A7 to the targeted tumor was investigated using athymic mice bearing human colon cancer, SW1116. Enalapril alone, which enhances tumor vascular permeability through the kinin-generating cascade, did not increase the uptake of 125I-labeled A7 (125I-A7) in SW1116 due to the systemic hypotension induced by its inhibitory effect on angiotensin converting enzyme. However, with combined angiotensin II (AT-II) and enalapril treatment, a 2-fold increase in the accumulation of 125I-A7 was seen when compared to A7 alone. This marked increase was presumably due to increased tumor vascular permeability induced by enalapril combined with the absence of hypotension due to the actions of AT-II. This approach might be useful in radioimmunodetection and immunotargeting chemotherapy using monoclonal antibody.
Noguchi
A
A
First Department of Surgery, Kyoto Prefectural University of Medicine.
Takahashi
T
T
Yamaguchi
T
T
Kitamura
K
K
Noguchi
A
A
Tsurumi
H
H
Takashina
K
K
Maeda
H
H
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D003110:Colonic Neoplasms / Q000098:blood supply / Q000378:metabolism*; D004656:Enalapril / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude
D000911:Antibodies, Monoclonal; D000804:Angiotensin II; D004656:Enalapril