Skip to main content
NCBI home page
Cancer Immunology, Immunotherapy : CII logoLink to Cancer Immunology, Immunotherapy : CII
. 1990 May;32(3):185–190. doi: 10.1007/BF01771455

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

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
PMCID: PMC11038481  PMID: 2126988

Abstract

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.

Keywords: Monoclonal Antibody, Adenocarcinoma, Cancer Research, Interferon, Median Survival

Footnotes

Supported by the Veterans Administration Medical Center and by Public Health Services grant CA 45 232 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services

References

  • 1.Balch CM, Tilden AB, Dougherty PA, Cloud GA, Abo T. Heterogeneity of natural killer lymphocyte abnormalities in colon cancer patients. Surgery USA. 1984;95:63. [PubMed] [Google Scholar]
  • 2.Ernstoff MS, Kirkwood JM. Changes in the bone marrow of cancer patients treated with recombinant interferon alpha-2. Am J Med. 1984;76:593. doi: 10.1016/0002-9343(84)90282-1. [DOI] [PubMed] [Google Scholar]
  • 3.Foon KA, Schroff RW, Bunn PA, Mayer D, Abrams PG, Fer M, Ochs J, Bottino GC, Sherwin SA, Carlo DJ. Effects of monoclonal antibody therapy in patients with chronic lymphocytic leukemia. Blood. 1984;64:1085. [PubMed] [Google Scholar]
  • 4.Greiner JW, Hand PW, Noguchi P, Fisher PB, Pestka S, Schlom J. Enhanced expression of surface tumor-associated antigens on human breast and colon tumor cells after recombinant leukocyte α-interferon treatment. Cancer Res. 1984;44:3208. [PubMed] [Google Scholar]
  • 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, 1394 [DOI] [PubMed]
  • 6.Herlyn D, Herlyn M, Steplewski Z, Koprowski H. Monoclonal antibody in cell-mediated cytotoxicity against human melanoma and colorectal carcinoma. Eur J Immunol. 1979;9:657. doi: 10.1002/eji.1830090817. [DOI] [PubMed] [Google Scholar]
  • 7.Jain RK. Transport of molecules in the tumor interstitium: a review. Cancer Rep. 1987;47:3039. [PubMed] [Google Scholar]
  • 8.Kerbel RJ. Implications of immunological heterogeneity of tumors. Nature. 1979;280:358. doi: 10.1038/280358a0. [DOI] [PubMed] [Google Scholar]
  • 9.Khazaeli MB, Saleh MN, Wheeler RH, Huster WJ, Holden H, Carranto R, LoBuglio AF. Phase I trial of multiple large doses of murine monoclonal antibody CO17-1A: II. Pharmacokinetics and immune response. JNCI. 1988;80:937. doi: 10.1093/jnci/80.12.937. [DOI] [PubMed] [Google Scholar]
  • 10.Koprowski H, Herlyn D, Lubeck M, Defreitas E, Sears HF. Human anti-idiotype antibodies in cancer patients: is the modulation of the immune response beneficial for the patient? Proc Natl Acad Sci USA. 1984;81:216. doi: 10.1073/pnas.81.1.216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Kurzrock R, Quesada JR, Talpaz M, Hersh EM, Reuben JM, Sherwin SA, Gutterman JU. Phase I study of multiple dose intramuscularly administered recombinant gamma interferon. J Clin Oncol. 1986;4:1101. doi: 10.1200/JCO.1986.4.7.1101. [DOI] [PubMed] [Google Scholar]
  • 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 Phase I study of pharmacological and immunological effects of human lymphoblastoid interferon given to patients with cancer. Cancer Res. 1983;43:4458. [PubMed] [Google Scholar]
  • 13.Liu A, Robinson R, Murray E, Ledbetter J, Hellström I, Hellström K. Production of a mouse-human chimeric monoclonal antibody to CD20 with potent Fc-dependent biologic activity. J Immunol. 1987;139:3521. [PubMed] [Google Scholar]
  • 14.LoBuglio AF, Khazaeli MB, Lee J, Haynes A, Sumerel L, Mischak R, Spitler L. Pharmacokinetics and immune response to xomazyme-mel in melanoma patients. Antibody Immunoconjugate Radiopharmacol. 1988;1:305. [Google Scholar]
  • 15.LoBuglio AF, Saleh MN, Lee J, Khazaeli MB, Carrano R, Holden H, Wheeler RH. Phase I trial of multiple large doses of murine monoclonal antibody CO17-1A: I. Clinical aspects. JNCI. 1988;80:932. doi: 10.1093/jnci/80.12.932. [DOI] [PubMed] [Google Scholar]
  • 16.LoBuglio AF, Wheeler RH, Trang J, Haynes A, Rogers K, Harvey EB, Sun L, Ghrayeb J, Khazaeli MB. Mouse/human chimeric monoclonal antibody in man: kinetic and immune response. Proc Natl Acad Sci USA. 1989;86:4220. doi: 10.1073/pnas.86.11.4220. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Meeker TC, Lowder J, Maloney DG, Miller RA, Thielemans K, Warnke R, Levy R. A clinical trial of anti-idiotype therapy for B cell malignancy. Blood. 1985;65:1349. [PubMed] [Google Scholar]
  • 18.Metcalf D. The molecular biology and function of granulocyte-macrophage colony-stimulating factors. Blood. 1986;67:257. [PubMed] [Google Scholar]
  • 19.Miller RA, Maloney DG, Warnke R, Levy R. Treatment of a B cell lymphoma with monoclonal anti-idiotype antibody. N Engl J Med. 1982;306:517. doi: 10.1056/NEJM198203043060906. [DOI] [PubMed] [Google Scholar]
  • 20.Murray HW. Interferon gamma, the activated macrophage, and host defense against microbial challenge. Ann Int Med. 1988;108:595. doi: 10.7326/0003-4819-108-4-595. [DOI] [PubMed] [Google Scholar]
  • 21.Nathan CF, Horowitz CR, de la Harpe J, Vadhan-Raj S, Sherwin SA, Oettgen HF, Krown SE. Administration of recombinant interferon γ to cancer patients enhances monocyte secretion of hydrogen peroxide. Proc Natl Acad Sci USA. 1985;82:8686. doi: 10.1073/pnas.82.24.8686. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.O'Connell MJ, Ritts RA, Jr, Moertel CG, Schutt AJ, Sherwin SA. Recombinant interferon-γ lacks activity against metastatic colorectal cancer but increases serum levels of Ca 19-9. Cancer. 1989;63:1998. doi: 10.1002/1097-0142(19890515)63:10<1998::aid-cncr2820631022>3.0.co;2-l. [DOI] [PubMed] [Google Scholar]
  • 23.Schroff RW, Stevenson HC. Human immune responses to murine monoclonal antibodies. In: Foon KA, Morgan AC, editors. Monoclonal antibody therapy of human cancer. The Hague: Nijhoff; 1985. p. 121. [Google Scholar]
  • 24.Sears HG, Herlyn D, Steplewski Z, Koprowski H. Effects of monoclonal antibody immunotherapy in patients with gastrointestinal adenocarcinoma. J Biol Response Modif. 1984;3:138. [PubMed] [Google Scholar]
  • 25.Skoskiewicz MJ, Colvin RB, Schneegerger EE, Russell PS. Widespread and selective induction of major histocompatibility complex-determined antigens in vivo by γ interferon. J Exp Med. 1985;162:1645. doi: 10.1084/jem.162.5.1645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Smith KA. Interleukin-2: Inception, impact and implications. Science. 1988;240:1169. doi: 10.1126/science.3131876. [DOI] [PubMed] [Google Scholar]
  • 27.Steplewski Z, Lubeck MD, Koprowski H. Human macrophages armed with murine immunoglobulin gamma 2 a antibodies to tumors destroy human cancer cells. Science. 1983;221:865. doi: 10.1126/science.6879183. [DOI] [PubMed] [Google Scholar]
  • 28.Suzu S, Yokota H, Yamada M, Yanai N, Saito M, Kawashima T, Saito M, Takaku F, Motoyoshi K. Enhancing effect of human monocytic colony-stimulating factor on monocyte tumoricidal activity. Cancer Res. 1989;49:5913. [PubMed] [Google Scholar]
  • 29.Tweardy DJ, Fujiwara H, Scillian JJ, Ellner J. Concurrent enhancement of monocyte immunoregulatory properties and effector functions by recombinant interferon-γ. Cell Immunol. 1986;100:34. doi: 10.1016/0008-8749(86)90004-3. [DOI] [PubMed] [Google Scholar]
  • 30.Vadhan-Ray S, Cordon-Cardo C, Carswell E, Mintzer D, Dantis L, Duteau C, Templeton MA, Oettgen HF, Old LJ, Houghton AN. 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. 1988;6:1636. doi: 10.1200/JCO.1988.6.10.1636. [DOI] [PubMed] [Google Scholar]
  • 31.Wallach D, Fellous M, Revel M. Preferential effect of γ-interferon on the synthesis of HLA antigens and their mRNAs in human cells. Nature. 1982;299:833. doi: 10.1038/299833a0. [DOI] [PubMed] [Google Scholar]
  • 32.Weiner LM, Moldofsky PJ, Gatenby RA, O'Dwyer J, O'Brien J, Litwin S, Comis RL. 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. 1988;48:2568. [PubMed] [Google Scholar]

Articles from Cancer Immunology, Immunotherapy : CII are provided here courtesy of Springer

RESOURCES