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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1992 Mar;83(3):240–243. doi: 10.1111/j.1349-7006.1992.tb00093.x

Enhanced Tumor Localization of Monoclonal Antibody by Treatment with Kininase II Inhibitor and Angiotensin II

Akinori Noguchi 1,, Toshio Takahashi 1, Toshiharu Yamaguchi 1, Kazuya Kitamura 1, Akira Noguchi 1, Hiroshi Tsurumi 1, Ken‐ichiroh Takashina 1, Hiroshi Maeda 2
PMCID: PMC5918801  PMID: 1582884

Abstract

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, SVV1116. Enalapril alone, which enhances tumor vascular permeability through the kinin‐generating cascade, did not increase the uptake of 125 I‐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.

Keywords: Key words, Monoclonal antibody A7, Vascular permeability, Kinin generating cascade, Kininase II inhibitor, Angiotensin II

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REFERENCES

  • 1. ) Pietersz , G. A. , Kanellos , J. , Smyth , M. J. , Zalcberg , J. and McKenzie , I. F. C.The use of monoclonal antibody conjugates for the diagnosis and treatment of cancer . Immunol. Cell Biol , 65 , 111 – 125 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 2. ) Takahashi , T. , Yamaguchi , T. , Kitamura , K. , Suzuyama , H. , Honda , M. , Yokota , T. , Kotanagi , T. , Takahashi , M. and Hashimoto , Y.Clinical application of monoclonal antibody drug conjugates for immunotargeting chemotherapy of colorectal carcinoma . Cancer , 61 , 25 – 33 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 3. ) Jain , R. K.Physiological barriers to delivery of monoclonal antibodies and other macromolecules in tumors . Cancer Res. , 50 ( Suppl. ), 814s – 819s ( 1990. ). [PubMed] [Google Scholar]
  • 4. ) Cobb , L. M.Intratumor factors influencing the access of antibody to tumor cells . Cancer Immunol. Immunother. , 28 , 235 – 240 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5. ) Matsumura , Y. , Kimura , M. , Yamamoto , T. and Maeda , H.Involvement of the kinin‐generating cascade in enhanced vascular permeability in tumor tissue . Jpn. J. Cancer Res. , 79 , 1327 – 1334 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6. ) Matsumura , Y. , Maruo , K. , Kimura , M. , Yamamoto , T. , Konno , T. and Maeda , H.Kinin‐generating cascade in advanced cancer patients and in vitro study . Jpn. J. Cancer Res. , 82 , 732 – 741 ( 1991. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7. ) Kotanagi , H. , Takahashi , T. , Masuko , T. , Hashimoto , Y. and Koyama , K.A monoclonal antibody against human colon cancers . Tohoku J. Med. , 148 , 353 – 360 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 8. ) Kitamura , K. , Takahashi , T. , Yamaguchi , T. , Yokota , T. , Noguchi , A. , Amagai , T. and Imanishi , J.Immunochemical characterization of the antigen recognized by the murine monoclonal antibody A7 against colorectal cancer . Tohoku J. Exp. Med. , 157 , 83 – 93 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 9. ) Suzuki , M‐ , Hori , K. , Abe , I. , Saito , S. and Sato , H.A new approach to cancer chemotherapy. Selective enhancement of tumor blood flow with angiotensin II . J. Natl. Cancer Inst. , 67 , 663 – 669 ( 1981. ). [PubMed] [Google Scholar]
  • 10. ) Abe , I. , Hori , K. , Saito , S. , Tanda , S. , Li , Y. and Suzuki , M.Increased intratumor concentration of fluorescein‐isothiocyanate‐labeled neocarzinostatin in rats under angiotensin‐induced hypertension . Jpn. J. Cancer Res. , 79 , 874 – 879 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11. ) Baba , T. and Taniguchi , S.Improvement of angiotensin II hypertension cancer chemotherapy . Jpn. J. Cancer Chemother. , 14 , 971 – 977 ( 1987. ) ( in Japanese ). [PubMed] [Google Scholar]
  • 12. ) Kalofonos , H. , Rowlinson , G. and Epenetos , A. A.Enhancement of monoclonal antibody uptake in human colon tumor xenografts following irradiation . Cancer Res. , 50 , 159 – 163 ( 1990. ). [PubMed] [Google Scholar]
  • 13. ) Cope , D. A. , Dewhirst , M. W. , Friedman , H. S. , Bigner , D. D. and Zalutsky , M. R.Enhanced delivery of a monoclonal antibody F(ab′)2 fragment to subcutaneous human glioma xenografts using local hyperthermia . Cancer Res. , 50 , 1803 – 1809 ( 1990. ). [PubMed] [Google Scholar]
  • 14. ) Gridley , D. S. , Ewart , K. L. , Cao , J. D. and Stickney , D. R.Hyperthermia enhances localization of 111in‐labeled hapten to bifunctional antibody in human colon tumor xenografts . Cancer Res. , 51 , 1515 – 1520 ( 1991. ). [PubMed] [Google Scholar]
  • 15. ) Smyth , M. J. , Pietersz , G. A. and McKenzie , F. C.Use of vasoactive agents to increase tumor perfusion and the antitumor efficacy of drug‐monoclonal antibody conjugates . J. Natl. Cancer Inst , 79 , 1367 – 1373 ( 1987. ). [PubMed] [Google Scholar]
  • 16. ) Russel , S. M. , Krauer , K. G. , McKenzie , F. C. and Pietersz , G. A.Effect of tumor necrosis factor on the antitumor efficacy and toxicity of aminopterin‐monoclonal antibody conjugates: parameters for optimization of therapy . Cancer Res. , 50 , 6028 – 6033 ( 1990. ). [PubMed] [Google Scholar]
  • 17. ) LeBerthon , B. , Khawli , L. A. , Alauddin , M. , Miller , G. K. , Charak , B. S. , Mazumder , A. and Epstein , A. L.Enahnced tumor uptake of macromolecules induced by a novel vasoactive interleukin 2 immunoconjugate . Cancer Res. , 51 , 2694 – 2698 ( 1991. ). [PubMed] [Google Scholar]

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