Development and Shelf-Life Determination of Recombinant Interleukin-2 (Proleukin)

  • John Geigert
  • Nicholas Solli
  • Peggy Woehleke
  • Sriram Vemuri
Part of the Pharmaceutical Biotechnology book series (PBIO, volume 5)


Human interleukin-2 (IL-2), formerly known as T cell growth factor (TCGF), is a growth and/or differentiation factor for a variety of immunologically active cells including T cells, B cells, natural killer (NK) cells, lympho-kine-activated killer cells, and macrophages (Doyle et al., 1985; Ralph et al., 1987).


Protein Purity Quality Control Department Coulometric Karl Fischer Titration Intramolecular Disulfide Linkage 
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  1. Blackstock, W. P., Dennis, R. J., Lane, S. J., Sparks, J. I., and Weir, M. P., 1988, The analysis of recombinant interleukin-2 by thermospray liquid chromatography-mass spectrometry, Anal. Biochem. 175:319–326.PubMedCrossRefGoogle Scholar
  2. Browning, J. L., Mattaliano, R. J., Chow, E. P., Liang, S. M., Allet, B., Rosa, J., and Smart, J. E., 1986, Disulfide scrambling of interleukin-2: HPLC resolution of the three possible isomers, Anal. Biochem. 155:123–128.PubMedCrossRefGoogle Scholar
  3. Doyle, M. V., Lee, M. T., and Fong, S., 1985, Comparison of the biological activities of human recombinant interleukin-2125 and native interleukin-2, J. Biol. Response Modifiers 4:96–109.Google Scholar
  4. Fernandes, P. M., and Lundblad, J. L., 1980, Preparation of a stable intravenous gamma-globulin: Process design and scale up, Vox Sang. 39:101–112.PubMedCrossRefGoogle Scholar
  5. Fernandes, P., and Taforo, T. A., 1986, Pharmaceutical compositions of microbially produced interleukin-2, U.S. Patent No. 4,604,377.Google Scholar
  6. Ferrara, P., Pecceu, F., Marchese, E., Vita, N., Roskam, W., and Lupker, J., 1987, Characterization of recombinant glycosylated human interleukin-2 produced by a recombinant plasmid transformed CHO cell line, FEBS 226:47–52.CrossRefGoogle Scholar
  7. Fisher, B. V., and Porter, P. B., 1981, Stability of bovine insulin, J. Pharm. Pharmacol. 33:203–206.PubMedCrossRefGoogle Scholar
  8. Gearing, A. J. H., and Thorpe, R., 1988, The international standard for human IL-2: Calibration by international collaborative study, J. Immunol. Methods 114:3–9.PubMedCrossRefGoogle Scholar
  9. Grote, W., Klaar, J., Muhlradt, P. F., and Monner, D. A., 1987, Large scale production and purification of human IL-2 from buffy coat lymphocytes stimulated with 12-O-tetradecanoyl-phorbol 13-acetate and calcium ionophore A23187, J. Immunol. Methods 103:15–25.PubMedCrossRefGoogle Scholar
  10. Kato, K., Yamada, T., Kawahara, K., Onda, H., Asano, T., Sugino, H., and Kaki-numa, A., 1985, Purification and characterization of recombinant human interleukin-2 produced in Escherichia coli, Biochem. Biophys. Res. Commun. 130:692–699.PubMedCrossRefGoogle Scholar
  11. Kenny, W. C., Watson, E., Bartley, T., Boone, T., and Altrock, B. W., 1986, Parameters for the evaluation of IL-2 stability, Lymphokine Res. 5:S23-S27.Google Scholar
  12. Kunitani, M., Hirtzer, P., Johnson, D., Halenbeck, R., Boosman, A., and Koths, K., 1986, Reversed-phase chromatography of interleukin-2 muteins, J. Chroma-togr. 359:391–402.CrossRefGoogle Scholar
  13. Lahm, H. W., and Stein, S.,1985, Characterization of recombinant human interleukin-2 with micromethods, J. Chromatogr. 326:357–361.PubMedCrossRefGoogle Scholar
  14. Landgraf, B., Cohen, F. E., Smith, K. A., Gadski, R., and Ciardelli, T. L., 1989, Structural significance of the C-terminal amphophilic helix of interleukin-2, J. Biol.Chem. 264:816–822.PubMedGoogle Scholar
  15. Marchese, E., Vita, N., Maureaud, T., and Ferrara, P., 1990, Separation by cation-exchange high-performance liquid chromatography of three forms of Chinese hamster ovary cell-derived recombinant interleukin-2, J. Chromatogr. 504: 351–358.PubMedCrossRefGoogle Scholar
  16. Ralph, P., Nakoinz, L, Doyle, M., Lee, M. T., Jeong, G., Haienbeck, R., Mark, D. F., and Koths, K., 1987, Human B and T lymphocyte stimulating properties of interleukin-2 (IL-2) muteins, in: Immune Regulation by Characterized Polypeptides, Liss, New York, pp. 453–462.Google Scholar
  17. Robb, R. J., 1985, Human interleukin-2, Methods Enzymol 116:493–525.PubMedCrossRefGoogle Scholar
  18. Ross, P. D., Finlayson, J. S., and Shrake, A., 1984, Thermal stability of human albumin measured by differential scanning colorimetry, Vox Sang. 47:19–27.PubMedCrossRefGoogle Scholar
  19. Sasaoki, K., Hiroshima, T., Kusumoto, S., and Nishi, K., 1989, Oxidation of methionine residues of recombinant human interleukin-2 in aqueous solutions, Chem. Pharm. Bull. 37:2160–2164.PubMedCrossRefGoogle Scholar
  20. Tada, H., Shiho, O., Kurshima, K. I., Koyama, M., and Tsukamoto, K., 1986, An improved colorimetric assay for interleukin-2, J. Immunol. Methods 93: 157–165.PubMedCrossRefGoogle Scholar
  21. Wang, A., Lu, S. D., and Mark, D. F., 1984, Site-specific mutagenesis of the human interleukin-2 gene: Structure-function analysis of the cysteine residues, Science 224:1431–1433.PubMedCrossRefGoogle Scholar
  22. Watson, E., and Kenny, W. C., 1988, High-performance size-exclusion chromatography of recombinant derived proteins and aggregated species, J. Chromatogr. 436:289–298.PubMedCrossRefGoogle Scholar
  23. Weber, D. V., and Bailon, P., 1990, Application of receptor-affinity chromatography to bioaffinity purification, J. Chromatogr. 510:59–69.PubMedCrossRefGoogle Scholar
  24. Yamada, T., Fujishima, A., Kawahara, K., Kato, K., and Nishimura, O., 1987, Importance of disulfide linkage for constructing the biologically active human interleukin-2, Arch. Biochem. Biophys. 257:194–199f.PubMedCrossRefGoogle Scholar
  25. Yamaka, T., Kato, K. Kawahara, K., and Nishimura, O., 1986, Separation of recombinant human interleukin-2 and methionyl interleukin-2 produced in Escherichia coli, Biochem. Biophys. Res. Commun. 135:837–843.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • John Geigert
    • 1
  • Nicholas Solli
    • 1
  • Peggy Woehleke
    • 1
  • Sriram Vemuri
    • 2
  1. 1.Quality Control DepartmentChiron CorporationEmeryvilleUSA
  2. 2.Scios Nova Inc.Mountain ViewUSA

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