Potentiation of Anti-Tumor Efficacy Resulting from the Combined Administration of Interferon α and of an Anti-Breast Epithelial Monoclonal Antibody in the Treatment of Breasl Cancer Xenografts

  • Luciano Ozzello
  • Carolyn M. DeRosal
  • Edward W. Blank
  • Kari Cantell
  • David V. Habif
  • Roberto L. Ceriani


It has been previously shown that natural interferons(nIFNS) and-α and -γ delivered intralesionally(IL) to xenografts of human breast carcinomas in nude mice exerted a greater inhibitory effect than when they were administered systemically(1). Similarly, in patients with advanced malignant melanoma treated with IL injections of IFNα the local anti-tumoreffects were found to be significantly greater than the systemic effects(2). These observations suggest that the success of IFN therapy may depend, at least in part, on the ability to concentrate the IFN in the target tissue. Unfortunately, to achieve high local concentrations of IFN without causing undesirable side effects is difficult because IFNs are rapidly eliminated. Therefore, it would be desirable to devise means by which IFNs could be selectively delivered to tumors and retained in them for long periods of ti me. This might be possible by coupling IFNs to monoclonal antibodies(MoAbs) directed against antigens specifically expressed by the tumor cells.


Human Breast Carcinoma Advanced Malignant Melanoma Human Breast Cancer Xenograft Human Leukocyte Interferon Human Mammary Carcinoma Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    L. Ozzello, D.V. Habif, C.M. DeRosa, and K. Cantell, Treatment of human breast cancer xenografts using natural interferons α and-l<Math> injected singly or in combination, J. Interferon Res. 8:679(1988)PubMedCrossRefGoogle Scholar
  2. 2.
    P. von Wussow, B. Berthold, F. Hartmann, and H. Deicher, Intralesional interferon-alpha therapy in advanced malignant melanoma, Cancer 61 :1071(1988).CrossRefGoogle Scholar
  3. 3.
    S.S. Alkan, S. Miescher-Granger, D.G. Braun, and H.K. Hochkeppel, Anti vi ral and antiproliferative effects of interferons delivered via monoclonal antibodies, J.Interferon Res. 4:355(1984).PubMedCrossRefGoogle Scholar
  4. 4.
    R. Tran, P. Horan Hand, J.W. Greiner, S. Pestka, and J. Schlom, Enhancement of surface antigen expression on human breast carcinoma cells by recombinant human interferons, J.Interferon Res. 8:75(1988).PubMedCrossRefGoogle Scholar
  5. 5.
    J.W. Greiner, F. Guadagni, P. Noguchi, S. Pestka, D. Colcher, P.B. Fisher, and J. Schlom, Recombinant interferon enhances monoclonal antibody-targeting of carcinoma lesions in vivo, Science 235:895(1987).PubMedCrossRefGoogle Scholar
  6. 6.
    R.L. Ceriani, E.W. Blank, and J.A. Peterson, Experimental immunotherapy of human breast carcinomas implanted in nude mice with a mixture of monoclonal antibodies against human milk fat globule components, Cancer Res. 47:532(1987).PubMedGoogle Scholar
  7. 7.
    R.L. Ceriani, and E.W. Blank, Experimental therapy of human breast tumors with 131I_labeled monoclonal antibodies against the human milk fat globule, Cancer Res. 48:4664(1988).PubMedGoogle Scholar
  8. 8.
    K. Cantell, S. Hirvonen, H.-L. Kauppinen and G. Myllyla, Production of interferon in human leukocytes from normal donors with the use of Sendai virus, Methods Enzymol. 78:29(1981).PubMedCrossRefGoogle Scholar
  9. 9.
    K. Cantell, S. Hirvonen, and H.-L. Kauppinen, Production and partial purification of human immune interferon, Methods Enzymol. 119:54(1986).PubMedCrossRefGoogle Scholar
  10. 10.
    H.-L. Kauppinen, S. Hirvonen, and K. Cantell, Effect of purification procedures on the composition of human leukocyte interferon preparations, Methods Enzymol. 119:27(1986).PubMedCrossRefGoogle Scholar
  11. 11.
    R.L. Ceriani, J.A. Peterson, J.Y. Lee, R. Moncada, and E.W. Blank, Characterization of cell surface antigens of human mammary epithelial cells with monoclonal antibodies prepared against human milk fat globule.Som. Cell Gen. 9:415(1983).CrossRefGoogle Scholar
  12. 12.
    J.L. Dickerson, J.J. Kornuc, and D.C. Rees, Complex formation between Flavodoxin and Cytochrome c.J. Biol. Chem. 260:5175(1985).PubMedGoogle Scholar
  13. 13.
    L. Ozzello, D.V. Habif, C.M. DeRosa, and K. Cantell, Effects of intralesional injections of interferons α on xenografts of human mammary carcinomacells(BT 20 and MCF-7), J. Interferon Res. 8:208(1988).Google Scholar
  14. 14.
    S.S. Alkan, H. Towbin, and H.K. Hochkeppel, Enhanced antiproliferative action of interferon targeted by bispecific monoclonal antibodies, J. Interferon Res. 8:25(1988).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1989

Authors and Affiliations

  • Luciano Ozzello
    • 1
  • Carolyn M. DeRosal
    • 1
  • Edward W. Blank
    • 2
  • Kari Cantell
    • 3
  • David V. Habif
    • 4
  • Roberto L. Ceriani
    • 2
  1. 1.Division of Surgical PathologyColumbia-Presbyterian Medical CenterNew YorkUSA
  2. 2.John Muir Cancer and Aging Research InstituteWalnut CreekUSA
  3. 3.National Public Health InstituteHelsinkiFinland
  4. 4.Department of SurgeryColumbia-Presbyterian Medical CenterNew YorkUSA

Personalised recommendations