Cancer Immunology, Immunotherapy

, Volume 32, Issue 3, pp 185–190 | Cite as

A phase II trial of murine monoclonal antibody 17-1A and interferon-γ: Clinical and immunological data

  • Mansoor N. Saleh
  • Albert F. LoBuglio
  • Richard H. Wheeler
  • Kimberly J. Rogers
  • Amy Haynes
  • Jeannette Y. Lee
  • M. B. Khazaeli
Original articles


A group of 15 patients with metastatic colorectal adenocarcinoma received a combination of interferon γ (0.1 mg/m2, days 1–15) and the murine monoclonal antibody 17-1A (400 mg, days 5, 7, 9 and 12). The treatment was tolerated with minimal toxicity. Of the 14 evaluable patients, 13 developed human antibody to murine 17-1A, with 11 patients demonstrating antibody to the variable region of 17-1A (anti-idiotype). Antibody to the variable region was inhibited by 17-1A but not by mouse immunoglobulin. Sera from patients with substantial anti-idiotype reactivity were capable of inhibiting the binding of murine 17-1A to antigen expressing LS174-T cells thus indicating the presence of antibody directed against the 17-1A combining site (mirror-image anti-idiotype). The median survival of the whole group was 56 weeks and there was no correlation between clinical response/survival and the development of anti-idiotype antibody.


Monoclonal Antibody Adenocarcinoma Cancer Research Interferon Median Survival 
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.


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  1. 1.
    Balch CM, Tilden AB, Dougherty PA, Cloud GA, Abo T (1984) Heterogeneity of natural killer lymphocyte abnormalities in colon cancer patients. Surgery USA 95: 63Google Scholar
  2. 2.
    Ernstoff MS, Kirkwood JM (1984) Changes in the bone marrow of cancer patients treated with recombinant interferon alpha-2. Am J Med 76: 593PubMedGoogle Scholar
  3. 3.
    Foon KA, Schroff RW, Bunn PA, Mayer D, Abrams PG, Fer M, Ochs J, Bottino GC, Sherwin SA, Carlo DJ (1984) Effects of monoclonal antibody therapy in patients with chronic lymphocytic leukemia. Blood 64: 1085PubMedGoogle Scholar
  4. 4.
    Greiner JW, Hand PW, Noguchi P, Fisher PB, Pestka S, Schlom J (1984) Enhanced expression of surface tumor-associated antigens on human breast and colon tumor cells after recombinant leukocyte α-interferon treatment. Cancer Res 44: 3208PubMedGoogle Scholar
  5. 5.
    Hale G, Clark MR, Marcus R, Winter G, Dyer MJS, Phillips JM, Riechmann L, Waldmann H (1988) Remission induction in non-Hodgkin lymphoma with reshaped human monoclonal antibody compath-1H. Lancet, 1394Google Scholar
  6. 6.
    Herlyn D, Herlyn M, Steplewski Z, Koprowski H (1979) Monoclonal antibody in cell-mediated cytotoxicity against human melanoma and colorectal carcinoma. Eur J Immunol 9: 657PubMedGoogle Scholar
  7. 7.
    Jain RK (1987) Transport of molecules in the tumor interstitium: a review. Cancer Rep 47: 3039Google Scholar
  8. 8.
    Kerbel RJ (1979) Implications of immunological heterogeneity of tumors. Nature 280: 358PubMedGoogle Scholar
  9. 9.
    Khazaeli MB, Saleh MN, Wheeler RH, Huster WJ, Holden H, Carranto R, LoBuglio AF (1988) Phase I trial of multiple large doses of murine monoclonal antibody CO17-1A: II. Pharmacokinetics and immune response. JNCI 80: 937PubMedGoogle Scholar
  10. 10.
    Koprowski H, Herlyn D, Lubeck M, Defreitas E, Sears HF (1984) Human anti-idiotype antibodies in cancer patients: is the modulation of the immune response beneficial for the patient? Proc Natl Acad Sci USA 81: 216PubMedGoogle Scholar
  11. 11.
    Kurzrock R, Quesada JR, Talpaz M, Hersh EM, Reuben JM, Sherwin SA, Gutterman JU (1986) Phase I study of multiple dose intramuscularly administered recombinant gamma interferon. J Clin Oncol 4: 1101PubMedGoogle Scholar
  12. 12.
    Laszlo J, Huang AT, Brenckman WD, Jeffs C, Koren H, Cianciolo G, Metzgar R, Cashdollar W, Cox E, Buckley CE III, Tso CY, Lucas VS Jr (1983) Phase I study of pharmacological and immunological effects of human lymphoblastoid interferon given to patients with cancer. Cancer Res 43: 4458PubMedGoogle Scholar
  13. 13.
    Liu A, Robinson R, Murray E, Ledbetter J, Hellström I, Hellström K (1987) Production of a mouse-human chimeric monoclonal antibody to CD20 with potent Fc-dependent biologic activity. J Immunol 139: 3521PubMedGoogle Scholar
  14. 14.
    LoBuglio AF, Khazaeli MB, Lee J, Haynes A, Sumerel L, Mischak R, Spitler L (1988) Pharmacokinetics and immune response to xomazyme-mel in melanoma patients. Antibody Immunoconjugate Radiopharmacol 1: 305Google Scholar
  15. 15.
    LoBuglio AF, Saleh MN, Lee J, Khazaeli MB, Carrano R, Holden H, Wheeler RH (1988) Phase I trial of multiple large doses of murine monoclonal antibody CO17-1A: I. Clinical aspects. JNCI 80: 932PubMedGoogle Scholar
  16. 16.
    LoBuglio AF, Wheeler RH, Trang J, Haynes A, Rogers K, Harvey EB, Sun L, Ghrayeb J, Khazaeli MB (1989) Mouse/human chimeric monoclonal antibody in man: kinetic and immune response. Proc Natl Acad Sci USA 86: 4220PubMedGoogle Scholar
  17. 17.
    Meeker TC, Lowder J, Maloney DG, Miller RA, Thielemans K, Warnke R, Levy R (1985) A clinical trial of anti-idiotype therapy for B cell malignancy. Blood 65: 1349PubMedGoogle Scholar
  18. 18.
    Metcalf D (1986) The molecular biology and function of granulocyte-macrophage colony-stimulating factors. Blood 67: 257PubMedGoogle Scholar
  19. 19.
    Miller RA, Maloney DG, Warnke R, Levy R (1982) Treatment of a B cell lymphoma with monoclonal anti-idiotype antibody. N Engl J Med 306: 517PubMedGoogle Scholar
  20. 20.
    Murray HW (1988) Interferon gamma, the activated macrophage, and host defense against microbial challenge. Ann Int Med 108: 595PubMedGoogle Scholar
  21. 21.
    Nathan CF, Horowitz CR, de la Harpe J, Vadhan-Raj S, Sherwin SA, Oettgen HF, Krown SE (1985) Administration of recombinant interferon γ to cancer patients enhances monocyte secretion of hydrogen peroxide. Proc Natl Acad Sci USA 82: 8686PubMedGoogle Scholar
  22. 22.
    O'Connell MJ, Ritts RA Jr, Moertel CG, Schutt AJ, Sherwin SA (1989) Recombinant interferon-γ lacks activity against metastatic colorectal cancer but increases serum levels of Ca 19-9. Cancer 63: 1998PubMedGoogle Scholar
  23. 23.
    Schroff RW, Stevenson HC (1985) Human immune responses to murine monoclonal antibodies. In: Foon KA, Morgan AC (eds) Monoclonal antibody therapy of human cancer. Nijhoff, The Hague, p 121Google Scholar
  24. 24.
    Sears HG, Herlyn D, Steplewski Z, Koprowski H (1984) Effects of monoclonal antibody immunotherapy in patients with gastrointestinal adenocarcinoma. J Biol Response Modif 3: 138Google Scholar
  25. 25.
    Skoskiewicz MJ, Colvin RB, Schneegerger EE, Russell PS (1985) Widespread and selective induction of major histocompatibility complex-determined antigens in vivo by γ interferon. J Exp Med 162: 1645PubMedGoogle Scholar
  26. 26.
    Smith KA (1988) Interleukin-2: Inception, impact and implications. Science 240: 1169PubMedGoogle Scholar
  27. 27.
    Steplewski Z, Lubeck MD, Koprowski H (1983) Human macrophages armed with murine immunoglobulin gamma 2 a antibodies to tumors destroy human cancer cells. Science 221: 865PubMedGoogle Scholar
  28. 28.
    Suzu S, Yokota H, Yamada M, Yanai N, Saito M, Kawashima T, Saito M, Takaku F, Motoyoshi K (1989) Enhancing effect of human monocytic colony-stimulating factor on monocyte tumoricidal activity. Cancer Res 49: 5913PubMedGoogle Scholar
  29. 29.
    Tweardy DJ, Fujiwara H, Scillian JJ, Ellner J (1986) Concurrent enhancement of monocyte immunoregulatory properties and effector functions by recombinant interferon-γ. Cell Immunol 100: 34PubMedGoogle Scholar
  30. 30.
    Vadhan-Ray S, Cordon-Cardo C, Carswell E, Mintzer D, Dantis L, Duteau C, Templeton MA, Oettgen HF, Old LJ, Houghton AN (1988) Phase I trial of a mouse monoclonal antibody against GD3 ganglioside in patients with melanoma: induction of inflammatory responses at tumor sites. J Clin Oncol 6: 1636PubMedGoogle Scholar
  31. 31.
    Wallach D, Fellous M, Revel M (1982) Preferential effect of γ-interferon on the synthesis of HLA antigens and their mRNAs in human cells. Nature 299: 833PubMedGoogle Scholar
  32. 32.
    Weiner LM, Moldofsky PJ, Gatenby RA, O'Dwyer J, O'Brien J, Litwin S, Comis RL (1988) Antibody delivery and effector cell activation in a phase II trial of recombinant γ-interferon and the murine monoclonal antibody CO17-1A in advanced colorectal carcinoma. Cancer Res 48: 2568PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • Mansoor N. Saleh
    • 1
    • 2
  • Albert F. LoBuglio
    • 1
  • Richard H. Wheeler
    • 1
  • Kimberly J. Rogers
    • 1
  • Amy Haynes
    • 1
  • Jeannette Y. Lee
    • 1
  • M. B. Khazaeli
    • 1
    • 2
  1. 1.The Comprehensive Cancer CenterUniversity of Alabama at BirminghamBirminghamUSA
  2. 2.Veterans Administration Medical CenterBirminghamUSA

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