Interferon Hybrids: Prospects for Therapy

  • Nowell Stebbing
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 166)


Recombinant DNA techniques have led to determination of the structure of human interferons and production of individual molecular species of interferon free from other species and other proteins simultaneously induced in human cell cultures. Comparison of the properties of different molecular species of interferon and molecular hybrids between the various species has indicated the extent to which the various biological properties of interferons may be separated. This information provides a basis for considering the design of particular molecular constructions of interferons with particular desired properties. The production of hybrid interferons from different genes with common restriction enzyme sites provides a method for producing desirable analogs. The current data are here reviewed with respect to potential clinical utility of such materials.


Antiviral Activity Antiviral Effect Human Interferon Human Cell Culture Individual Molecular Species 
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.
    Nagata, S., H. Tiara, A. Hall, L. Johnsrud, M. Streuli, J. Escodi, W. Boll, K. Cantell, and C. Weissmann. 1980. Synthesis in E. coli of a polypeptide with human leukocyte interferon activity. Nature 284: 316–320.PubMedCrossRefGoogle Scholar
  2. 2.
    Goeddel, D. V., D. W. Leung, T. J. Dull, M. Gross, R. M. Lawn, R. McCandliss, P. H. Seeburg, A. Ullrich, E. Yelverton, and P. W. Gray. 1981. The structure of eight distinct cloned human leukocyte interferon cDNAs. Nature 390: 20–26.CrossRefGoogle Scholar
  3. 3.
    Franke, A. E., H. M. Shepard, C. M. Houck, P. W. Leung, D. V. Goeddel, and R. M. Lawn. 1982. Carboxy terminal region of hybrid leukocyte interferons affects antiviral specificity. DNA (in press).Google Scholar
  4. 4.
    Wetzel, R., L. J. Perry, D. A. Estell, N. Lin, H. L. Levine, B. Slinker, F. Fields, M. J. Ross, and J. Shively. 1981. Properties of a human alpha interferon purified from E. coli extracts. J. Interferon Res. 1: 381–390.PubMedCrossRefGoogle Scholar
  5. 5.
    Wetzel, R., H. L. Levine, D. A. Estell, S. Shive, J. Finer-Moore, R. M. Stroud, and T. A. Bewley. 1982. Structure-function studies on human alpha interferon. In T. Merigan and R. Friedman (eds.), Chemistry and biology of interferons: Relationship to therapeutics. UCLA Symp. Mol. Cell. Biol. 25, Academic Press, New York (in press).Google Scholar
  6. 6.
    Pitha, P. M., D. L. Slate, N. B. K. Raj, and R. H. Ruddle. 1982. Human ß1 interferon gene localization and expression in somatic cell hybrids. Mol. Cell. Biol. 2: 564–570.PubMedGoogle Scholar
  7. 7.
    Gray, P. W., D. W. Leung, D. Pennica, E. Yelverton, E. Najarian, C. C. Simonsen, R. Derynck, P. J. Sherwood, D. M. Wallace, S. L. Berger, A. D. Levinson, and D. V. Goeddel. 1982. Expression of human immune interferon cDNA in E. coli and monkey cells. Nature 295: 503–508.PubMedCrossRefGoogle Scholar
  8. 8.
    Allen, G., and K. H. Fantes. 1980. A family of structural genes for human lymphoblastoid (leukocyte-type) interferon. Nature 287: 408–411.PubMedCrossRefGoogle Scholar
  9. 9.
    Harkins, R. N., P. E. Hass, W. H. Kohr, B. B. Aggarwal, P. K. Weck, and S. Apperson. 1982. Structural and biological properties of purified bacteria derived human fibroblast interferon. Proc. Natl. Acad. Sci. (in press).Google Scholar
  10. 10.
    Shepard, H. M., D. Leung, N. Stebbing, and D. V. Goeddel. 1981. A single amino acid change in human fibroblast interferon (IFN-βl) abolishes antiviral activity. Nature 294: 563–565.PubMedCrossRefGoogle Scholar
  11. 11.
    Weck, P. K., S. Apperson, E. Hamilton, and N. Stebbing. 1982. Biological properties of genetic hybrids of bacteria-derived human leukocyte interferons. J. Cell. Biochem. Suppl. 6: 104.Google Scholar
  12. 12.
    Weck, P. K., S. Apperson, N. Stebbing, P. W. Gray, D. Leung, H. M. Shepard, and D. V. Goeddel. 1981. Antiviral activities of hybrids of two major human leukocyte interferons. Nucleic Acids Res. 9: 6153–6166.PubMedCrossRefGoogle Scholar
  13. 13.
    Masucci, M. G., R. Szigeti, E. Klein, G. Klein, J. Gruest, L. Montagnier, H. Taira, A. Hall, S. Nagata, and C. Weissmann. 1980. Effect of interferon-al from E. coli on some cell functions. Science 209: 1431–1435.PubMedCrossRefGoogle Scholar
  14. 14.
    Weck, P. K., S. Apperson, L. May, and N. Stebbing. 1981. Comparison of the antiviral activity of various cloned human inter-feron-a subtypes in mammalian cell cultures. J. Gen Virol. 57: 233–237.PubMedCrossRefGoogle Scholar
  15. 15.
    Lee, S. H., S. Kelley, H. Chiu, and N. Stebbing. 1982. Stimulation of natural killer cell activity and inhibition of proliferation of various leukemic cells by purified human leukocyte interferon subtypes. Cancer Res. 42: 1312–1316.PubMedGoogle Scholar
  16. 16.
    Weck, P. K., E. Rinderknecht, D. A. Estell, and N. Stebbing. 1982. Antiviral activity of bacteria derived human leukocyte interferons against encephalomyocarditis virus infection of mice. Infect. Immun. 35: 660–665.PubMedGoogle Scholar
  17. 17.
    Stebbing, N., P. K. Weck, J. T. Fenno, S. Apperson, and S. H. Lee. 1981. Comparison of the biological properties of natural and recombinant DNA derived human interferons, p. 25–33. In E. DeMaeyer, G. Galasso and H. Schellekens (eds.), The biology of the interferon system. Elsevier/North Holland.Google Scholar
  18. 18.
    Schellekens, H., W. Weimar, K. Cantell, and L. Stitz. 1979. Antiviral effect of interferon in vivo may be mediated by the host. Nature 278: 742.PubMedCrossRefGoogle Scholar
  19. 19.
    Stebbing, N., K. M. Dawson, and I. J. D. Lindley. 1978. Requirement for macrophages for interferon to be effective against encephalomyocarditis virus infection in mice. Infect. Immun. 19: 5–11.PubMedGoogle Scholar
  20. 20.
    Smolin, G., N. Stebbing, M. Friedlender, R. Friedlender, and M. Okumoto. 1982. Natural and cloned human leukocyte interferon in herpes virus infections of rabbit eyes. Arch. Ophthamol. 100: 481–483.CrossRefGoogle Scholar
  21. 21.
    Stebbing, N., P. K. Weck, J. T. Fenno, D. A. Estell, and E. Rinderknecht. 1982. Antiviral effects of bacteria derived human leukocyte interferons against encephalomyocarditis virus infection of squirrel monkeys. Arch. Virol. (in press).Google Scholar
  22. 22.
    Gresser, I., C. Maury, and D. Brouty-Boye. 1972. Mechanisms of the antitumor effect of interferon in mice. Nature 239: 167–168.PubMedCrossRefGoogle Scholar
  23. 23.
    Stebbing, N., S. H. Lee, B. J. Marafino, P. K. Weck, and K. W. Renton. 1982. Activity of cloned gene products in animal systems. In F. Ahmad, J. Schultz and E. E. Smith (eds.), From gene to protein: Translation into biotechnology. Academic Press, New York (in press).Google Scholar
  24. 24.
    Singh, G., K. W. Renton, and N. Stebbing. 1982. Homogeneous interferon from E. coli depresses hepatic cytochrome P-450 and drug biotransformation. Biochem. Biophys. Res. Commun. 106: 1256–1261.PubMedCrossRefGoogle Scholar
  25. 25.
    Hengst, J. C. D., M. B. Mokyr, and S. Dray. 1981. Cooperation between cyclophosphamide tumoricidal activity and host antitumor immunity in the cure of mice bearing large MOPC-315 tumors. Cancer Res. 41: 2163–2167.PubMedGoogle Scholar
  26. 26.
    Branca, A. A., and C. Baglioni. 1981. Evidence that types I and II interferons have different receptors. Nature 294: 768–770.PubMedCrossRefGoogle Scholar
  27. 27.
    Chany, C. 1976. Membrane-bound interferon specific cell receptor system: role in the establishment and amplification of the antiviral state. Biomedicine 24: 148–157.PubMedGoogle Scholar
  28. 28.
    Streuli, M., A. Hall, W. Boll, W. E. Stewart, S. Nagata, and C. Weissmann. 1981. Target cell specificity of two species of human interferon-a produced in Escherichia coli and of hybrid molecules derived from them. Proc. Nat. Acad. Sci. 78: 2848–2852.PubMedCrossRefGoogle Scholar
  29. 29.
    Levy, W. P., M. Rubinstein, J. Shively, V. D. Valle, C. Y. Lai, J. Moschera, L. Brink, L. Gerber, S. Stein, and S. Pestka. 1981. Amino acid sequence of a human leukocyte interferon. Proc. Nat. Acad. Sci. 78: 6186–6190.PubMedCrossRefGoogle Scholar
  30. 30.
    Lee, S. H., P. K. Weck, J. Moore, S. Chen, and N. Stebbing. 1982. Pharmacological comparison of two hybrid recombinant DNA derived human leukocyte interferons. In T. Merigan and R. Friedman (eds.), Chemistry and biology of interferons: Relationship to therapeutics. UCLA Symp. Mol. Cell. Biol. 25, Academic Press, New York (in press).Google Scholar
  31. 31.
    Moore, J. A., B. J. Marafino, and N. Stebbing. 1982. Influence of various purified interferons on pharmacological effects of drugs in mice. J. Path. (in press).Google Scholar

Copyright information

© Springer Science+Business Media New York 1983

Authors and Affiliations

  • Nowell Stebbing
    • 1
  1. 1.AMGen, Inc.Thousand OaksUSA

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