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. 1994 Jul;39(4):263–268. doi: 10.1007/BF01525990

Neutralizing interferon β antibodies in melanoma patients treated with recombinant and natural interferon β

Gerhard Fierlbeck 1,✉, Tilmann Schreiner 1, Bernd Schaber 1, Anton Walser 2, Gernot Rassner 1
PMCID: PMC11038129  PMID: 7954528

Abstract

The incidence and clinical significance of therapy-induced neutralizing interferon β (IFNß) antibodies was studied in a group of 21 melanoma patients treated with natural IFNß and 7 patients treated with recombinant IFNß. They were treated subcutaneously with 3×106 IU three times per week in an adjuvant open trial for 24 weeks after surgical removal of all detectable metastases. Of the 21 patients treated with natural IFNß, 95% developed significant levels of neutralizing antibodies after 24 weeks. In comparison, 28% of the 7 patients treated with recombinant IFNß developed neutralizing IFNß antibodies. Cross-reactivity of the antibodies could be demonstrated. Persistence of antibody titers was seen in 80% of the patients 24 weeks after cessation of treatment with natural IFNß. No correlation between the maximum antibody titers and the antibody persistence after cessation of therapy could be established. We detected a clear correlation between the formation of neutralizing antibodies and the decrease in β2-microglobulin and 2′,5′-oligoadenylate synthease and therefore the drop in biological activity. In this adjuvant trial there was no difference in relapse rate and time until relapse between antibody-positive and antibody-negative patients. No difference in clinical outcome could be established between the patients treated with natural IFNß and recombinant IFNß.

Key words: Melanoma, Interferon β, Antibodies, Adjuvant trial

References

  • 1.Antenelli G, currenti M, Turriziani MO, Dianzani F. Neutralizing antibodies to IFN-α: relative frequency in patients treated with different interferon preparations. J Interferon Res. 1990;163:882–885. doi: 10.1093/infdis/163.4.882. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Conrad HS, Egge H, Katalinic JP, Reiser W, Siklosi T, Schaper K. Structure of the carbohydrate moiety of human interferon-β secreted by a recombinant Chinese hamster ovary cell line. J Biol Chem. 1987;262:14600–14605. [PubMed] [Google Scholar]
  • 3.Dummer R, Müller W, Nestle F, Wiede J, Dues J, Lechner W, Haubitz I, Wolf W, Bill E, Burg G. Formation of neutralizing antibodies against natural interferon β but not against recombinant interferon γ during adjuvant therapy for high-risk malignant melanoma patients. Cancer. 1991;67:2300–2304. doi: 10.1002/1097-0142(19910501)67:9<2300::aid-cncr2820670916>3.0.co;2-a. [DOI] [PubMed] [Google Scholar]
  • 4.Fierlbeck G, Hoedt B d', Stroebel W, Mayer P, Rassner G. Adjuvante Therapie des malignen Melanoms mit IFN-beta im klinischen Stadium II. Zentralbl Haut. 1993;162:115. [Google Scholar]
  • 5.Figlin R, Itri L. Anti interferon antibodies: A perspective. Sem Hematol. 1988;25:9–15. [PubMed] [Google Scholar]
  • 6.Fineberg SE, Galloway JA, Fineberg NS, Fineberg NS, Rathbun MJ, Hufferad S. Immunogenicity of recombinant DNA human insulin. Diabetologica. 1983;25:465–469. doi: 10.1007/BF00284452. [DOI] [PubMed] [Google Scholar]
  • 7.Hirata Y. Insulin and autoimmunity in a case of spontaneous hypoglycaemia. J Jpn Diabetic Soc. 1979;13:31. [Google Scholar]
  • 8.Kaplan S, Sarvag D, Suter S (1973) Antibodies to hGH arising in patients treated with hGH: incidence, characteristics and effect on growth, In: Rati S (ed) Advances in hGH research. DHEW 74-612. US Government Printing Office Washington, DC, pp 725–744
  • 9.Kirkwood IM, Ernstoff MS. Role of INFs in the therapy of melanoma. J Invest Dermatol. 1990;95:180–184. doi: 10.1111/1523-1747.ep12875497. [DOI] [PubMed] [Google Scholar]
  • 10.Larocca A, Leung SC, Marcus SG. Evaluation of neutralizing antibodies in patients treated with recombinant interferon betaser. J Interferon Res. 1989;9:551–560. [PubMed] [Google Scholar]
  • 11.Laruso A. Natural antibodies to IFNγ in man and their increase during viral infection. J Immunol. 1990;144:685–690. [PubMed] [Google Scholar]
  • 12.Lee J, Vilcek J. Biology of disease, Interleukin-6: a multifunctional cytokine regulating immune reactions and the acute phase protein response. Lab Invest. 1989;61:588–602. [PubMed] [Google Scholar]
  • 13.Monson RT. Malignant melanoma: a plaque of our times. Br J Surg. 1989;76:997–998. doi: 10.1002/bjs.1800761003. [DOI] [PubMed] [Google Scholar]
  • 14.Moosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. Immunol Methods. 1983;65:55–63. doi: 10.1016/0022-1759(83)90303-4. [DOI] [PubMed] [Google Scholar]
  • 15.Oberg K, Magnusson A, Lundquist G, Theodorson E, Wide L, Wilander E. Treatment of malignant carcinoid tumors with recombinant interferon alpha 2b: Development of neutralizing interferon antibodies and possible loss of antitumor activity. J Natl Cancer Inst. 1989;81:531–534. doi: 10.1093/jnci/81.7.531. [DOI] [PubMed] [Google Scholar]
  • 16.Prümmer O. Interferon alpha antibodies in patients with renal cell carcinoma treated with recombinant interferon alpha 2A in an adjuvant multicenter trial. Cancer. 1993;71:1828–1834. doi: 10.1002/1097-0142(19930301)71:5<1828::aid-cncr2820710518>3.0.co;2-0. [DOI] [PubMed] [Google Scholar]
  • 17.Quesada JR. Antitumor activity of recombinant-derived Interferon α in metastatic renal cell carcinoma. J Clin Oncol. 1985;3:1522–1528. doi: 10.1200/JCO.1985.3.11.1522. [DOI] [PubMed] [Google Scholar]
  • 18.Quesada JR, Itri L, Gutterman J. Alpha interferons in hairy cell leukaemia. A five year follow-up in 100 patients. J Interferon Res. 1987;7:678. [Google Scholar]
  • 19.Reiser W, Hauser H. Recombinant human interferon-β from mammalian cell lines. Arzneimittelforschung. 1987;37:482–485. [Google Scholar]
  • 20.Robbins J, Rall JE, Rawson RW. An unusual instance of thyroxin binding by human serum gamma globulin. J Clin Endocrinol Metab. 1956;16:573–579. doi: 10.1210/jcem-16-5-573. [DOI] [PubMed] [Google Scholar]
  • 21.Ross C, Hansen MB, Schyberg T, Berg K. Autoantibodies to crude human leucocyte interferon (IFN), native human IFN, recombinant human IFNα 2b and human IFNγ in healthy blood donors. Clin Exp Immunol. 1990;82:57–62. doi: 10.1111/j.1365-2249.1990.tb05403.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Steinberg IJ, Huang P, Ljubich P, Lee Huang S. Antierythropoetin antibodies in hypervisosity syndrome associated with giant lymph-node hyperplasia (GLNA: Castleman's disease) Br J Haematol. 1990;74:543–544. doi: 10.1111/j.1365-2141.1990.tb06351.x. [DOI] [PubMed] [Google Scholar]
  • 23.Steis RG, Smith JW, Urban WJ. Resistance of recombinant interferon α 2a in hairy cell leukemia associated with neutralizing anti interferon antibodies. N Engl J Med. 1988;318:1409–1413. doi: 10.1056/NEJM198806023182201. [DOI] [PubMed] [Google Scholar]
  • 24.Vallbracht A, Treuner J, Flehmig B, Joesster KE, Niethammer D. Interferon-neutralizing antibodies in a patient treated with human fibroblast interferon. Nature. 1981;289:496–497. doi: 10.1038/289496a0. [DOI] [PubMed] [Google Scholar]
  • 25.Wilkinson M, McElduff A, Wilson J, Haber P, Freeman A, Robertson M, Mathews P. Spontaneously occurring antibodies to parathyroid hormone. J Clin Endocrinol Metab. 1990;70:1744–1749. doi: 10.1210/jcem-70-6-1744. [DOI] [PubMed] [Google Scholar]
  • 26.Wolvekamp MC, Marquet RL. Interleukin-6: historical background, genetics and biological significance. Immunol Lett. 1990;24:1–10. doi: 10.1016/0165-2478(90)90028-o. [DOI] [PubMed] [Google Scholar]
  • 27.von Wussow P, Jakschies D. Interferon-Antikörper-Phantasie oder Faktum. In: Niederle N, von Wussow P, editors. Interferone: präklinische und klinische. Berlin Heidelberg New York: Springer; 1990. pp. 79–91. [Google Scholar]

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