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Recombinant Proteins of Therapeutic Interest Expressed by Lymphoid Cell Lines Derived from Transgenic Mice

Abstract

As a new approach to produce human proteins of therapeutic interest we have derived lymphoid cell lines expressing such proteins from transgenic mice, either by generating trans-hybridomas by cell fusion in vitro or by onc gene-mediated immortalisation in vivo of transgenic lymphocytes. The latter procedure could be applied to different cell types for the expression of proteins that require tissue-specific modifications.

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References

  1. Yelton, D.E., Marguhes, D.H., Diamond, B., and Scharff, M.D. 1980. Plasmacytomas and hybridomas development and applications, p. 3–17. In: Monoclonal antibodies. Hybridomas: a new dimension in biological analyses. Kennet, R. H., McKearn, T. J., and Bechtol, K. B. (Eds). Plenum Press, New York and London.

    Chapter  Google Scholar 

  2. Storb, U. 1987. Transgenic mice with immunoglobulin genes. Ann. Rev. Immunol. 5:151–174.

    Article  CAS  Google Scholar 

  3. Babinet, C., Morello, D., Rougeot, C., and Rouyre, S. 1986. Transhybridomas from fusion gene transgenic lymphocytes can be used to produce foreign protein of biological interest. Eur. J. Immunol. 16:1033–1035.

    Article  CAS  PubMed  Google Scholar 

  4. Owen, M.C., Brennan, S.O., Lewis, J.H., and Carrell, R.W. 1983. Mutation of antitrypsin to antithrombin. α1-antitrypsin Pittsburgh (358 Met→Art), a fatal bleeding disorder. N. Engl. J. Med. 309:694–698.

    Article  CAS  PubMed  Google Scholar 

  5. Courtney, M., Jallat, S., Tessier, L.-H. et al. 1985. Synthesis in E. coli of α1-antitrypsin variants of therapeutic potential for emphysema and thrombosis. Nature 313:149–151.

    Article  CAS  PubMed  Google Scholar 

  6. Schapira, M., Ramus, M.-A., Jallat, S., Carvallo, D., and Courtney, M. 1986. Recombinant α1-antitrypsin Pittsburgh (Met358→Arg) is a potent inhibitor for plasma kallikrem and activated factor XII fragment. J. Clin. Invest. 77:635–637.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Thompson, A.R. 1986. Structure, function and molecular defects of factor IX. Blood 67:565–572.

    CAS  PubMed  Google Scholar 

  8. De la Salle, H., Altenburger, W., Elkaim, R. et al. 1985. Active γ-carboxylated human factor IX expressed using recombinant DNA techniques. Nature 316:268–270.

    Article  CAS  PubMed  Google Scholar 

  9. Balland, A., Faure, T., Carvallo, D. et al. 1988. Characterization of two differently processed forms of human recombinant factor IX synthesized in CHO cells transformed with a polycistronic vector. Eur. J. Biochem. 172:565–572.

    Article  CAS  PubMed  Google Scholar 

  10. Garver, R.I., Chytil, A., Karlsson, S. et al. 1987. Production of glycosylated physiologically “normal” human α1-antitrypsin by mouse fibroblasts modified by insertion of a human α1-antitrypsin cDNA using a retroviral vector. Proc. Natl. Acad. Sci. USA 84:1050–1054.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Straight, D.L., Sherill, G.B., Noyes, C.M. et al. 1985. Structural and functional characteristics of activated human factor IX after chemical modification of γ-carboxyglutamic acid residues. J. Biol. Chem. 260:2890–2894.

    CAS  PubMed  Google Scholar 

  12. Rabiet, M.-J., Jorgensen, M.J., Furie, B., and Furie, B.C. 1987. Effect of propeptide mutations on post-translational processing of factor IX. J. Biol. Chem. 262:14895–14898.

    CAS  PubMed  Google Scholar 

  13. Banerji, J., Olson, L., and Schaffner, W. 1983. A lymphocyte-specific cellular enhancer is located downstream of the joining region in immunoglobulin heavy-chain genes. Cell 33:729–740.

    Article  CAS  PubMed  Google Scholar 

  14. Gillies, S.S., Morrison, S.L., Di, V.T., and Tonegawa, S. 1983. A tissue-specific transcription enhancer element is located in the major intron of a rearranged immunoglobulin heavy-chain gene. Cell 33:717–728.

    Article  CAS  PubMed  Google Scholar 

  15. Adams, J.M., Harris, C.A., Pinkert, L.M. et al. 1985. The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice. Nature 318:533–538.

    Article  CAS  PubMed  Google Scholar 

  16. Ornitz, D.M., Hammer, R.E., Messing, A., Palmiter, R.D., and Brinster, R.L. 1987. Pancreatic neoplasia induced by SV40 T-antigen expression in acinar cells of transgenic mice. Science 238:188–193.

    Article  CAS  PubMed  Google Scholar 

  17. Neuberger, M.S. 1983. Expression and regulation of immunoglobulin heavy-chain gene transfected into lymphoid cells. EMBO J. 2:1373–1378.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Bernard, O., Cory, S., Gerondakis, S., Webb, E., and Adams, J.M. 1983. Sequence of the murine and human cellular myc oncogenes and two modes of myc transcription resulting from chromosome translocation in B lymphoid tumours. EMBO J. 2:2375–2383.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Brinster, R.L., Chen, H.Y., Messing, A. et al. 1984. Transgenic harboring SV40 T-antigen genes develop characteristic brain tumours. Cell 37:367–379.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Weidle, U.H. and Buckel, P. 1987. Establishment of stable mouse myeloma cells constitutively secreting human tissue-type plasminogen activator. Gene 57:131–141.

    Article  CAS  PubMed  Google Scholar 

  21. Hendricks, M.B., Banker, M.J., and McLaughlin, M. 1988. A high-efficiency vector for expression of foreign genes in myeloma cells. Gene 64:43–51.

    Article  CAS  PubMed  Google Scholar 

  22. Suda, Y., Aizawa, S., Hirai, S. et al. 1987. Driven by the same Ig enhancer and SV40 T promoter ras induced lung adenomatous tumours, myc induced pre-B cell lymphomas and SV40 large T gene a variety of tumors in transgenic mice. EMBO J. 6:4055–4065.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Maniatis, F., Fritsch, F., and Sambrook, J. 1982. Molecular Cloning, a Laboratory Manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY.

    Google Scholar 

  24. Kelley, D.E., Coleclough, C., and Perry, R.P. 1982. Functional significance and evolutionary development of the 5′-terminal regions of immunoglobulin variable-regions genes. Cell 29:681–689.

    Article  CAS  PubMed  Google Scholar 

  25. Krawinkel, U., Zoebelien, G., and Bothwell, A.L.M. 1986. Palindromic sequences are associated with sites of DNA breakage during gene conversion. Nucl. Acids Res. 14:3871–3882.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Chase, T. and Shaw, E. 1970. Titration of trypsin, plasmin and thrombin with p-nitrophenyl p′-guanidinobenzoate HC1. Methods Enzymol. 19:20–27.

    Article  Google Scholar 

  27. Meunier, L., Allain, J.P., and Frommel, D. 1975. Performances of an artificial reagent for the one-stage factor IX assay. Thromb. Diath. Haemorrh. 33:547–552.

    Article  CAS  PubMed  Google Scholar 

  28. St. Groth, F.S. and Scheidegger, D. 1980. Production of monoclonal antibodies: strategy and tactics. J. Immunol. Methods 35:1–21.

    Article  Google Scholar 

  29. Meulien, P., Faure, T., Mischler, F. et al. 1988. A new recombinant procoagulant protein derived from the cDNA encoding human FVIII. Protein Engineering 2:301–306.

    Article  CAS  PubMed  Google Scholar 

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Pavirani, A., Skern, T., Meur, M. et al. Recombinant Proteins of Therapeutic Interest Expressed by Lymphoid Cell Lines Derived from Transgenic Mice. Nat Biotechnol 7, 1049–1054 (1989). https://doi.org/10.1038/nbt1089-1049

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