Individually Specified Drug Immunoconjugates in Cancer Treatment

  • Robert K. Oldham
  • Shuen-Kuei Liao
  • John R. Ogden
  • William H. Hubbard


Forty-three patients, including 13 patients with metastatic breast cancer, each received an individuallyspecified combination of either Adriamycin(24 patients) or mitomycin-C(19 patients) conjugated murine monoclonal ant ibodies. Tumors were typed using a panel of antibodies with both immunohistochemistry and flow cytometry. Cocktails composed of 2–6 antibodies were selected based on binding greater than 80% of the malignant cells in the biopsy specimen. These monoclonal antibody cocktails were drug conjugated and administered intravenously.

Seventeen out of twenty-four patients had reactions (fever, chills, pruritis and skin rash) to the administration of Adriamycin immunoconjugates, but these were tolerable in all but two patients. In several patients it was demonstrated that there was limited antigenic drift among various biopsies within the same patient over time. Up to 1 gram of Adriamycin and up to 5 grams of monoclonal antibody were administered. Two patients with breast carcinoma had depinite improvement in ulcerating skin lesions. The limiting factor appeared to be a variable dissociation of active Adriamycin from the antibody which unpredictably caused hemopoietic depression.

Similar findings were noted in 19 patients with mitomycin-C conjugates. Thrombocytopenia at a 60mg dose of mitomycin-C in this schedule was dose limiting. Preliminary serological evidence suggests that the development of an IgM antibody which is specific against the mouse monoclonal antibody has the specificity and sensitivity to predict clinical reactions. These antibodies were quantitatively less in mitomycin-C than Adriamycin treated patients.


Breast Cancer Breast Carcinoma Murine Monoclonal Antibody Nude Mouse Xenograft Antibody Selection 
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  1. 1.
    Bernhard, M.I., Hwang, K.M., Foon, K.A. et al.: Localization of Indium and Iodine-Labeled Monoclonal Ant ibod ies in Guinea Pigs Bearing Line 10 Hepatocarcino-ma Tumors.Cancer Research 43 :4429–4433, 1983.PubMedGoogle Scholar
  2. 2.
    Goldenberg, D.M., De Land, F. H.: History and Status of Tumor Imaging and Radiolabeled Antibodies: J. Biol. Resp. Modif. 1: 121–136, 1982.Google Scholar
  3. 3.
    Avner, B. P., Liao, S.K., Avner, B., et al.: Therapeutic Murine Monoclonal Antibodies Developed for Individual Cancer Patients. J. Biol. Resp. Modif. (In Press), 1988.Google Scholar
  4. 4.
    Liao, S.K., Meranda, C., Avner, B.P., et al.: Immunohistochemical Phenotyping of Human Solid Tumors with Monoclonal Antibodies in Devising Biotherapeutic Strategies.Cancer Immunol. and Immunother.(In Press) 1989.Google Scholar
  5. 5.
    Ogden, J.R., Leung, K. Kunda, S.A., Telander, M.W., Avner, B. P., Liao, S.K., Thurman, G.B., Oldham, R.K.: Immunoconj uga tes of Doxorub ic in and Murine Anti-Human Breast Carcinoma Monoclonal Antibodies Prepared via an N-Hydroxysucc in imide Active Ester Intermediate of Cisaconityl Doxorubicin: Preparation and In Vivo Cytoxicity. Molecular Biotherapy (In Press). 1988Google Scholar
  6. 6.
    Orr, D.W., Oldham, R.K., and Lewis, M.: Phase I Trial of Mitomycin-C Immunoconj uga tes. (In Preparation), 1988.Google Scholar
  7. 7.
    Avner, B. P., Gaydos, B., Liao, S.K., Thurman, G.B., Oldham, R.K.: Characterization of a Method Using Viable Human Target Cells as the Solid Phase in a Cell Concentration Fluorescent Immunoassay(CCFIA) for Screening of Monoclonal Antibodies and Hybridoma Supernatants. J. Immunol. Meth. 113: 123–135, 1988.CrossRefGoogle Scholar
  8. 8.
    Avner, B., Swindell, L., Sharp, E., Liao, S.K., Avner, B. P., Oldham, R.K.: Monitoring of Patient Immune Reponses to Intravenous Therapy with Murine Monoclonal Antibodies Conjugated to Adriamyc in: Relevance to Clinical Events. Cancer Research(Submitted). 1988Google Scholar
  9. 9.
    Oldham, R.K., Lewis, M., Orr, D.W., Avner, B. P., Liao, S.K., Ogden, J., Avner, B., and Birch, R.: Adriamycin Custom-Tailored Immunoconjugates in the Treatment of Human Malignancies.Molecular Biotherapy(In Press), 1988.Google Scholar
  10. 10.
    Houghton, A., Mintzer, D., Cordon-Cardo, C., et al: Mouse Monoclonal IgG-3 Antibody Detecting GD-3 Ganglioside: A Phase I Trial in Patients with Malignant Melanoma.Proc. Natl. Acad. Sci. (USA), 82 :1242–1246, 1985.CrossRefGoogle Scholar
  11. 11.
    Oldham, R., Foon, K., Morgan, C., et al.: Monoclonal Antibody Therapy of Malignant Melanoma: In Vivo Locatl izat ion and Cutaneous Metastases After Intravenous Administration. J. Clin. Oncol. 2: 1235–1244, 1984.PubMedGoogle Scholar
  12. 12.
    De Nardo, S., De Nardo, G., O’Grady, L., et al: Pilot Studies of Radioimmunotherapy of B-Cell Lymphoma and Leukemia Using I-131 Lym-1 Monoclonal Antibody:Ant ibod. Immunoconj. Radiopharm. 1(1): 17 – 33, 1988.Google Scholar
  13. 13.
    Rosen, S., Zimmer, A., Goldman-Leikin, R., et al: Radioimmunodetection and Radioimmunotherapy of Cutaneous TCell Lymphomas Using I-311 — Labeled Monoclonal Antibody: An Illinois Cancer Counsel Study. J. Clinical Oncology 5(4): 562–73, 1987.Google Scholar
  14. 14.
    Epenetos, A., Monroe, A., Stewart, S., et al: Antibody Guided Radiation of Advanced Ovarian Cancer with Intraperitoneally Administered Radiolabeled Monoclonal Antibodies. J. Clin. Oncol. 5(12): 1890–1899, 1987.PubMedGoogle Scholar
  15. 15.
    Spitler, L., Del Rio, M., Khentizan, A., et al: Therapy of Patients with Malignant Melanoma Using a Monoclonal Anti-Melanoma Antibody-Ricin A Chain Immunotoxin:Cancer Research 47: 1717 –1723, 1987.PubMedGoogle Scholar
  16. 16.
    Oldham, R. K.: Monoclonal Antibodies — Does Suf f ic ient Selectivity to Cancer Cells Exist for Therapeutic Application? J. Biol. Resp. Modif. 6 :277–284, 1987.Google Scholar
  17. 17.
    Oldham, R.K.: Immunoconjugates — Drugs and Toxins. In: Oldham, R.K.(Ed.)Principles of Cancer Biotherapy. Raven Press, New York, pp. 319–335, 1987.Google Scholar

Copyright information

© Springer Science+Business Media New York 1989

Authors and Affiliations

  • Robert K. Oldham
    • 1
  • Shuen-Kuei Liao
    • 1
  • John R. Ogden
    • 1
  • William H. Hubbard
    • 1
  1. 1.Biotherapeutics, Inc.FranklinUSA

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