Skip to main content
SpringerLink
Log in

Low incidence of antibody formation due to long-term interferon-α2c treatment of cancer patients

  • Original Article
  • Published:
The clinical investigator Aims and scope Submit manuscript

Summary

In order to study the long-term immunogenicity of interferon-α2c (Berofor) in cancer patients, serum was collected starting in 1983 from study patients with various proliferative diseases who received interferon-α2c at different doses, according to different schedules, and via different routes. A total of 1992 samples were tested for the presence of anti-interferon-α2c antibodies. Due to long-term interferon-α2c treatment, 346 patients were eligible for induction of neutralizing anti-interferon antibodies over a treatment period of 252 months. Most patients were treated for longer than 6 months. Of the 346 patients, three patients (0.87%) exhibited measurable titers of neutralizing antibodies following therapy with interferon-α2c. One hundred and sixty-three patients suffered from non-Hodgkin lymphomas, leukemias, and preleukemias. One patient with chronic myeloid leukemia experienced antibody induction under therapy. The other 183 patients had solid tumors. Two of them reacted with antibody production. All titers were very low (1:12, 1:8, and 1:64). Compared with figures reported for other interferon-α preparations, the propensity of interferon-α2c to induce neutralizing antibodies seems to be very low. This property might be related to arginines occurring as critical residues in positions 23 and 34 of the interferon-α2c molecule.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

ANB:

antiviral neutralization bioassay

CE:

competitive sandwich ELISA

EBI:

Ernst Boehringer Institut

IFN:

interferon

References

  1. Bekisz JB, zur Nedden DL, Enterline JC, Zoon KC (1989) Antibodies to interferon-alpha 2 in patients treated with interferon-alpha 2 for hairy cell leukemia. J Interferon Res (Suppl 1) 9:S1-S7

    Google Scholar 

  2. Dworkin-Rastl E, Dworkin MB, Swetly P (1982) Molecular cloning of human alpha and beta interferon genes from Namalwa cells. J Interferon Res 2:575–585

    Google Scholar 

  3. Dworkin-Rastl E, Swetly P, Dworkin MB (1983) Construction of expression plasmids producing high levels of human leukocyte-type interferon in Escherichia coli. Gene 20:237–248

    Google Scholar 

  4. Figlin RA, Itri LM (1988) Anti-interferon antibodies: a perspective. Semin Hematol (Suppl 3) 25:9–15

    Google Scholar 

  5. Figlin RA, deKernion JB, Mukamel E, Palleroni AV, Itri LM, Sarna GP (1988) Recombinant interferon alfa-2a in metastatic renal cell carcinoma: assessment of antitumor activity and anti-interferon antibody formation. J Clin Oncol 6:1604–1610

    Google Scholar 

  6. Getzoff ED, Tainer JA, Lerner RA, Geysen HM (1988) The chemistry and mechanism of antibody binding to protein antigens. Adv Immunol 43:1–89

    Google Scholar 

  7. Geysen HM, Mason TJ, Rodda SJ (1988) Cognitive features of continuous antigenic determinants. J Mol Recognition 1:32–41

    Google Scholar 

  8. Inglada L, Porres JC, LaBanda F, Mora I, Carreno V (1987) Anti-IFN-alpha titres during interferon therapy. Lancet II 1521

    Google Scholar 

  9. Itri LM, Campion M, Dennin RA, Palleroni AV, Gutterman JU, Groopman JE, Trown PW (1987) Incidence and clinical significance of neutralizing antibodies in patients receiving recombinant interferon alfa-2a by intramuscular injection. Cancer 59:668–674

    Google Scholar 

  10. Itri LM, Sherman MI, Palleroni AV, Evans LM, Tran LL, Campion M, Chizzonite R (1989) Incidence and clinical significance of neutralizing antibodies in patients receiving recombinant interferon alfa-2a. J Interferon Res (Suppl 1) 9:S9-Sl6

    Google Scholar 

  11. Jacobs SL, Kelsey DK (1986) Antibodies in patients with hairy-cell leukemia receiving alpha-2b interferon. N Engl J Med 315:1418

    Google Scholar 

  12. Mogensen KE, Daubas Ph, Gresser I, Sereni D, Varet B (1981) Patient with circulating antibodies to alpha-interferon. Lancet II:1227–1228

    Google Scholar 

  13. Oberg K (1988) Long-term treatment with alpha interferons of patients with malignant carcinoid tumors - the six years experience. J Interferon Res (Suppl 1) 8:S22 (abstract)

    Google Scholar 

  14. Oberg K, Alm G (1989) Development of neutralizing interferon antibodies after treatment with recombinant interferon alfa-2b in patients with malignant carcinoid tumors. J Interferon Res (Suppl 1) 9:S45-S49

    Google Scholar 

  15. Panem S, Vilcek J (1983) Antibodies to interferon in man. In: De Mayer E, Schellekens H (eds) The biology of the interferon system. Elsevier, Amsterdam, pp 369–378

    Google Scholar 

  16. Panem S, Check IJ, Henriksen D, Vilcek J (1982) Antibodies to alpha-interferon in a patient with systemic lupus erythematosus. J Immunol 129:1–3

    Google Scholar 

  17. Prümmer O, Porzsolt F for the Delta-P Study Group (1991) Interferon (IFN)-alpha antibody formation during adjuvant IFN-alpha 2a treatment of renal cancer. VI. European Interferon Workshop, Hannover: How to optimize IFN-therapy, p 20 (abstract)

  18. Quesada JR, Itri L, Gutterman JU (1987) Alpha interferons in hairy cell leukemia (HCL): a five year follow up of 100 patients. J Interferon Res 67:678

    Google Scholar 

  19. Quesada JR, Rios A, Swanson D, Trown P, Gutterman JU (1985) Antitumor activity of recombinant-derived interferon alpha in metastatic renal cell carcinoma. J Clin Oncol 3:1522–1528

    Google Scholar 

  20. Schmidt H, Heidemann E, Vallbracht A, Waller HD (1985) Antibodies to human leukocyte interferon alpha after half a year of interferon treatment. Tumordiagn Ther 6:37–41

    Google Scholar 

  21. Spiegel RJ, Spicehandler JR, Jacobs SL, Oden EM (1986) Low incidence of serum neutralizing factor in patients receiving recombinant alfa-2b interferon (Intron A). Am J Med 80:223–228

    Google Scholar 

  22. Spiegel RJ, Jacobs SL, Treuhaft MW (1989) Anti-interferon antibodies to interferon alfa-2b: results of comparative assays and clinical perspective. J Interferon Res (Suppl 1): 9:S17–14

    Google Scholar 

  23. Steis RG, Smith II JW, Urba W, Clark JW, Itri LM, Evans LM, Schoenberger C, Longo DL (1988) Resistance to recombinant interferon alfa-2a in hairy cell leukaemia associated with neutralizing anti-interferon antibodies. N Engl J Med 318:1409–1413

    Google Scholar 

  24. Trown PW, Dennin Jr RA, Kramer MJ, Connell EV, Palleroni AV, Quesada J, Gutterman JU (1983) Antibodies to human leucocyte interferons in cancer patients. Lancet 1:81–84

    Google Scholar 

  25. Van Regenmortel MHV (1989) Structural and functional approaches to the study of protein antigenicity. Immunol Today 10:266–272

    Google Scholar 

  26. Von Wussow P, Freund M, Block B, Poliwoda H, Deicher H (1987) Clinical significance of anti-IFN-alpha antibody titres during interferon therapy. Lancet II:635–636

    Google Scholar 

  27. Von Wussow P, Freund M, Dahle S, Jakschies D, Poliwoda H, Deicher H (1988) Immunogenicity of different types of interferons in the treatment of hairy-cell leukemia. N Engl J Med 319:1226–1227

    Google Scholar 

  28. Von Wussow P, Jakschies D, Freund M, Deicher H (1989) Humoral response to recombinant interferon alfa-2b in patients receving recombinant interferon alfa-2b therapy. J Interferon Res (Suppl 1) 9:S25-S31

    Google Scholar 

  29. Von Wussow P, Pralle H, Jakschies D, Deicher H (1991) Resistance due to high-titered rIFN-alfa-antibodies can be overcome by nIFN-alpha in hairy cell leukemia. VI. Eurpean Interferon Workshop, Hannover: How to optimize IFN-therapy, p 23 (abstract)

  30. Week PK, Lewenthal BG, Brandt C, Finter NB (1989) Detection and incidence of neutralizing antibodies to interferon alfa-n1. J Interferon Res (Suppl 1) 9:S37-S43

    Google Scholar 

  31. World Health Organisation Expert Committee on Biological Standardization (1985) Standardization of interferons: Report of a WHO informal consultation. WHO, Geneva, Technical Report Series 725:29–64

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dr. Karl Thomae GmbH, Birkendorfer Strasse 65, W-7950, Biberach, Germany

    G. G. Steinmann

  2. Bender + Co. Ges mbH, Wien

    B. Göd, G. Adolf, B. Frühbeis, H. Lamche, J. Lindner, E. Patzelt & F. -J. Schneider

  3. Boehringer Ingelheim GmbH, Germany

    F. Rosenkaimer

  4. Bioscientia GmbH, Ingelheim

    G. Bidlingmaier & C. Schmähling

Authors
  1. G. G. Steinmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. Göd
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F. Rosenkaimer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G. Adolf
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G. Bidlingmaier
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. B. Frühbeis
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. H. Lamche
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. J. Lindner
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. E. Patzelt
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. C. Schmähling
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. F. -J. Schneider
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Steinmann, G.G., Göd, B., Rosenkaimer, F. et al. Low incidence of antibody formation due to long-term interferon-α2c treatment of cancer patients. Clin Investig 70, 136–141 (1992). https://doi.org/10.1007/BF00227355

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00227355

Key words

Search

Navigation