Skip to main content

Advertisement

Log in

Antibody engineering, a strategy for the development of monoclonal antibodies

  • Biotechnology
  • Published:
Antonie van Leeuwenhoek Aims and scope Submit manuscript

Abstract

Antibody engineering is the selection process enabling the isolation of hybridoma clones, each of which produces an antibody with predefined qualities. The state of the art of hybridoma technology is reviewed with emphasis on the results obtained by antibody engineering in our laboratories for the development of monoclonal antibodies for specific use in diagnostic tests. The perspective for in vitro monoclonal antibody production as well as the application of monoclonal antibodies for diagnostic reagents, industrial purification and therapeutic use are indicated.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Abrams, P. G., Knost, J. A., Clarke, G., Wilburn, S., Oldham, R. K. andFoon, K. A. 1983. Determination of the optimal human cell lines for development of human hybridomas. — J. Immunol.131: 1201–1204.

    CAS  PubMed  Google Scholar 

  • Bamezai, A. K. andTalwar, G. P. 1984. Use of monoclonals for purification of zona pellucida antigens and for generation of anti-idiotypic antibodies simulating the antigen. — 7th Int. Biotechnol. Symp. New Delhi, Abstr.1: 132.

    Google Scholar 

  • Bartholomew, R., Beidler, D. andDavid, G. 1982. Immunoaffinity chromatography with monoclonal antibodies. p. 667–670.In H. Peeters (ed.), Peptides of the Biological Fluids, Proc. 30th Colloq., Brussels. — Pergamon Press, Oxford.

    Google Scholar 

  • Bosch, A. M. G., Stevens, W., Schuurs, A., Schönherr, O. T. andRoelofs, H. W. M. 1980. Characteristics of monoclonal antibodies against human chorionic gonadotrophin (HCG). p. 837–842.In H. Peeters (ed.), Peptides of the Biological Fluids, Proc. 29th Colloq., Brussels. — Pergamon Press, Oxford.

    Google Scholar 

  • Boss, B. D. 1984. An improved in vitro immunization procedure for the production of monoclonal antibodies against neural and other antigens. — Brain Res.291: 193–196.

    Article  CAS  PubMed  Google Scholar 

  • Bouters, R., Moyaert, I., Coryn, M. andVandeplassche, M. 1983. The use of a PMSG antiserum in superovulated cattle: endocrinological changes and effects on timing of ovulation. — Zuchthygiene18: 172–177.

    Google Scholar 

  • Boyd, J. E., James, K. andMcClelland, D. B. L. 1984. Human monoclonal antibodies—production and potential. — Trends Biotechnol.2: 70–77.

    Article  CAS  Google Scholar 

  • Brenner, M. K., Newton, C. A., North, M. E., Weyman, C. andFarrant, J. 1983. The interaction of specific T cell help and nonspecific B cell growth factors in the production of anti-tetanus antibody by human B cells grown in serum-free microcultures. — Immunology50: 377–385.

    CAS  PubMed  Google Scholar 

  • Brocades-Zaalberg, O. andLubbe, F. H. 1984. Methods for the rapid selection of hybrid cells producing specific antibodies of high affinity. p. 251–257.In E. H. Houwink and R. R. van de Meer (eds), Innovations in Biotechnology, Prog. Ind. Microbiol., Vol. 20. — Elsevier, Amsterdam.

    Google Scholar 

  • Cabilly, S., Riggs, A. D., Pande, H., Shively, J. E., Holmes, W. E., Rey, M., Perry, L. J., Wetzel, R. andHeyneker, H. L. 1984. Generation of antibody activity from immunoglobulin polypeptide chains produced inEscherichia coli. — Proc. Natl Acad. Sci. USA81: 3273–3277.

    CAS  PubMed  Google Scholar 

  • Clark, M., Cobbold, S., Hale, G. andWaldmann, H. 1983. Advantages of rat monoclonal antibodies. — Immunol. Today4: 100–101.

    Article  Google Scholar 

  • Croce, C. M., Linnenbach, A., Hall, W., Steplewski, Z. andKoprowski, H. 1980. Production of human hybridomas secreting antibodies to measles virus. — Nature (London)288: 488–489.

    Article  CAS  Google Scholar 

  • Fasekas de St. Groth, S. 1983. Automated production of monoclonal antibodies in a cytostat. — J. Immunol. Methods57: 121–136.

    Google Scholar 

  • Fasekas de St. Groth, S. andScheidegger, D. 1980. Production of monoclonal antibodies: strategy and tactics. — J. Immunol. Methods35: 1–21.

    Google Scholar 

  • Foung, S. K. H., Perkins, S., Raubitschek, A., Larrick, J., Lizak, G., Fishwild, D., Engleman, E. G. andGrumet, F. C. 1984. Rescue of human monoclonal antibody production from an EBV-transformed B cell line by fusion to a human-mouse hybridoma. — J. Immunol. Methods70: 83–90.

    Article  CAS  PubMed  Google Scholar 

  • Goding, J. W. 1980. Antibody production by hybridomas. — J. Immunol. Methods39: 285–308.

    Article  CAS  PubMed  Google Scholar 

  • Goding, J. W. 1983. Monoclonal Antibodies: Principles and Practice. — Academic Press, London.

    Google Scholar 

  • Haaijman, J. J., Deen, C., Kröse, C. J. M., Zijlstra, J. J., Coolen, J. andRadl, J. (1984). Monoclonal antibodies in immunocytology, a jungle full of pitfalls. — Immunol. Today5: 56–58.

    Article  CAS  Google Scholar 

  • Herzenberg, L. A. andHerzenberg, L. A. 1978. Analysis and separation using the fluorescence activated cell sorter (FACS). Ch. 22.In D. M. Weir (ed.), Handbook of Experimental Immunology, Vol. 2. — Blackwell Scientific Publications, London.

    Google Scholar 

  • Hilgers, J. 1983. Hybridoma technology in cancer research. p. 85.In Biotechnological Research in The Netherlands, Poster Symp., Delft. — Netherlands Biotechnological Society.

  • Hoffman, R. A. andHansen, W. P. 1981. Immunofluorescent analysis of blood cells of flow cytometry. — Int. J. Immunopharmocol.3: 249–254.

    CAS  Google Scholar 

  • Jonak, Z. L., Braman, V. andKennett, R. H. 1983. Transfection of primary mouse lymphocytes with human tumor DNA: production of continuous cell lines producing monoclonal antibodies. — Hybridoma2: 124.

    Google Scholar 

  • Jonak, Z. L., Braman, V. andKennett, R. H. 1984. Production of continuous mouse plasma cell lines by transfection with human leukemia DNA. — Hybridoma3: 107–118.

    CAS  PubMed  Google Scholar 

  • Kearney, J. F., Radbruch, A., Liesegang, B. andRajewsky, K. 1979. A new mouse myeloma cell line that has lost immunoglobulin expression but permits the contruction of antibody-secreting hybrid cell lines. — J. Immunol.123: 1548–1550.

    CAS  PubMed  Google Scholar 

  • Khaw, B. A., Fallon, J. T., Beller, G. A. andHaber, E. 1979. Specificity of localization of myosinspecific antibody fragments in experimental myocardial infarction. — Circulation60: 1527–1531.

    CAS  PubMed  Google Scholar 

  • Khaw, B. A., Fallon, J. T., Strauss, H. W. andHaber, E. 1980. Myocardial infarct imaging of antibodies to canine cardiac myosin with indium-111-diethylenetriamine pentaacetic acid. — Science209: 295–297.

    CAS  PubMed  Google Scholar 

  • Klausner, A. 1983. Monoclonal makers upping production vying for new contracts. — Biotechnology1: 737–740.

    Google Scholar 

  • Knazek, R. A., Gullino, P. M., Kohler, P. O. andDedrick, R. L. 1972. Cell culture on artificial capillaries: an approach to tissue growth in vitro. — Science178: 65–67.

    CAS  PubMed  Google Scholar 

  • Köhler, G. andMilstein, C. 1975. Continuous cultures of fused cells secreting antibody of predefined specificity. — Nature (London)256: 495–497.

    Article  Google Scholar 

  • Kozbor, D. andRoder, J. C. 1983. The production of monoclonal antibodies from human lymphocytes. — Immunol. Today4: 72–79.

    Article  CAS  Google Scholar 

  • Ku, K., Kuo, M. J., Delente, J., Wildi, B. S. andFeder, J. 1981. Development of a hollow-fiber system for large-scale culture of mammalian cells. — Biotechnol. Bioeng.23: 79–95.

    Article  Google Scholar 

  • Lerner, R. A. 1982. Tapping the immunological repertoire to produce antibodies of predetermined specificity. — Nature (London)299: 592–596.

    Article  CAS  Google Scholar 

  • Lo, M. M. S., Tsong, T. Y., Conrad, M. K., Strittmatter, S. M., Hester, L. D. andSnyder, S. H. 1984. Monoclonal antibody production by receptor-mediated electrically induced cell fusion. — Nature (London)310: 792–794.

    Article  CAS  Google Scholar 

  • Mach, J. P., Buchegger, F., Forni, M., Ritschard, J., Berche, C., Lumbroso, J., Schreyer, M., Girardet, C., Accolla, R. S. andCarrel, S. 1982. Use of radiolabelled monoclonal anti-CEA antibodies for the detection of human carcinomas by external photoscanning and tomosintigraphy. — Immunol. Today2: 239–249.

    Google Scholar 

  • Merchant, B. 1983. Points to consider in the Manufacture of Monoclonal Antibody Products for Human Use. Draft Document by the Hybridoma Committee of the Office of Biologics. — Food and Drug Administration U.S.A.

  • Milstein, C. 1980. Monoclonal antibodies. — Sci. Am.243 (4): 56–64.

    Google Scholar 

  • Moldofsky, P. J., Powe, J., Mulhern, C. B. Jr., Hammond, N., Sears, H. F., Gatenby, R. A., Steplewski, Z. andKoprowski, H. 1983. Metastatic colon carcinoma detected with radiolabelled F(Ab)2 monoclonal antibody fragments. — Radiology149: 549–556.

    CAS  PubMed  Google Scholar 

  • Morein, B., Sundquist, B., Höglund, S., Dalsgaard, K. andOsterhaus, A. 1984. Iscom, a novel structure for antigenic presentation of membrane proteins from enveloped viruses. — Nature (London)308: 457–460.

    Article  CAS  Google Scholar 

  • Olsson, L. andKaplan, H. S. 1980. Human-human hybridomas producing monoclonal antibodies of predefined antigenic specificity. — Proc. Natl Acad. Sci. USA77: 5429–5431.

    CAS  PubMed  Google Scholar 

  • Olsson, L., Kronstroem, H., Cambon-De Mouzon, A., Honsik, C., Brodin, T. andJakobsen, B. 1983. Antibody producing human-human hybridomas. I. Technical aspects. — J. Immunol. Methods61: 17–32.

    Article  CAS  PubMed  Google Scholar 

  • Östberg, L. andPursch, E. 1983. Human × (mouse × human) hybridomas stably producing human antibodies. — Hybridoma2: 361–367.

    PubMed  Google Scholar 

  • Osterhaus, A. D. M. E., Van Wezel, A. L., Hazendonk, T. G., UytdeHaag, F. G. C. M., Van Asten, J. A. A. M. andVan Steenis, B. 1983a. Monoclonal antibodies to polioviruses. Comparison of intratypic strain differentiation of poliovirus type 1 using monoclonal antibodies versus cross-absorbed antisera. — Intervirology20: 129–136.

    CAS  PubMed  Google Scholar 

  • Osterhaus, A. D. M. E., Weijers, T. G., Bijlsma, K., De Ronde-Verloop, F. M., Van Asten, J. A. A. M. andDe Jong, J. C. 1983b. Comparison of monoclonal antibodies with ferret sera for the characterisation of influenza A (H3N2) virus strains in a computer system.In Monoclonal Antibodies: Standardization in their Production and Use, IABS Congress, Paris.

  • OTAreport, 1984. Commercial Biotechnology: an International Analysis. — Washington, D. C., U.S. Congress, Office of Technology Assessment, OTA-BA-218, Jan. 1984.

  • Parks, D. R., Bryan, V. M., Oi, V. T. andHerzenberg, L. A. 1979. Antigen-specific identification and cloning of hybridomas with a fluorescence-activated cell sorter. — Proc. Natl Acad. Sci. USA176: 1962–1966.

    Google Scholar 

  • Poste, G. andKirsh, R. 1983. Site-specific (targeted) drug delivery in cancer therapy. — Biotechnology1: 869–878.

    CAS  Google Scholar 

  • Prentice, H. G., Blacklock, H. A., Janossy, G., Bradstock, K. F., Skeggs, D., Goldstein, G. andHoffbrand, A. V. 1982. Use of anti-T-cell monoclonal antibody OKT3 to prevent acute graft-versus-host disease in allogeneic bone-marrow transplantation for acute leukaemia. — Lanceti: 700–703.

    Google Scholar 

  • Reading, C. L. 1982. Theory and methods for immunization in culture and monoclonal antibody production. — J. Immunol. Methods53: 261–291.

    Article  CAS  PubMed  Google Scholar 

  • Schlom, J., Wunderlich, D. andTeramoto, Y. A. 1980. Generation of human monoclonal antibodies reactive with human mammary carcinoma cells. — Proc. Natl Acad. Sci. USA77: 6841–6845.

    CAS  PubMed  Google Scholar 

  • Schönherr, O. T. andRoelofs, H. W. M. 1982. Monoclonal antibodies for diagnostic tests and affinity chromatography: a first step to antibody engineering. p. 235–242.In International Association of Biological Standardization (ed.), Proc. Joint Esact — IABS Meeting on the Use of Heteroploid and other Cell Substrates for the Production of Biologicals, Dev. Biol. Stand., Vol. 500. — S. Karger, Basel.

    Google Scholar 

  • Schönherr, O. T., Roelofs, H. W. M. andHouwink, E. H. 1984. Development screening and quality specifications of hybridomas synthesizing anti-polypeptide hormone antibodies to be used for diagnostic tests and in-process control. p. 163–171.In International Association of Biological Standardization (ed.), Fifth Gen. Meeting Eur. Soc. Animal Cell Technol., Dev. Biol. Stand., Vol. 55. — S. Karger, Basel.

    Google Scholar 

  • Secher, D. S. andBurke, D. C. 1980. A monoclonal antibody for large-scale purification of human leukocyte interferon. — Nature (London)285: 446–450.

    Article  CAS  Google Scholar 

  • Stähli, C., Staehelin, T., Miggiano, V., Schmidt, J. andHäring, P. 1980. High frequencies of antigen-specific hybridomas: dependence on immunization parameters and prediction by spleen cell analyses. — J. Immunol. Methods32: 297–304.

    PubMed  Google Scholar 

  • Steinitz, M., Klein, G., Koskimies, S. andMakel, O. 1977. EB virus-induced B lymphocyte cell lines producing specific antibody. — Nature (London)269: 420–422.

    Article  CAS  Google Scholar 

  • Sutcliffe, J. G., Shinnick, T. M., Green, N. andLerner, R. A. 1983. Antibodies that react with predetermined sites on proteins. — Science219: 660–666.

    CAS  PubMed  Google Scholar 

  • Tabin, C. J., Bradley, S. M., Bargmann, C. I., Weinberg, R. A., Papageorge, A. G., Scolnick, E. M., Dhar, R., Lowy, D. R. andChang, E. H. 1982. Mechanism of activation of a human oncogene. — Nature (London)300: 143–149.

    Article  CAS  Google Scholar 

  • Talwar, G. P. 1984. Hybridomas, a new dimension for immuno diagnostics and immuno therapy. — 7th Int. Biotechnol. Symp., New Delhi, Plenary Lecture (not published).

  • Teng, N. N. H., Lam, K. S., Clavo Riera, F. andKaplan, H. S. 1983. Construction and testing of mouse-human heteromyelomas for human monoclonal antibody production. — Proc. Natl Acad. Sci. USA80: 7308–7312.

    CAS  PubMed  Google Scholar 

  • Tsung, Y. K., Milkunsky, A. andAlpert, E. 1980. Derivation and characterization of a monoclonal hybridoma antibody specific for human alpha-fetoprotein. — J. Immunol. Methods.39: 363–368.

    Article  CAS  PubMed  Google Scholar 

  • Uytdehaag, F. G. C. M., Siebeling, C. H. J., Drost, G. A., Van Steenis, G. andOsterhaus, A. D. M. E. 1983. Immunization of mice against polio virus type 2 using anti-idiotypic antibody. p. 84.In Biotechnological Research in The Netherlands, Poster Symp., Delft. — Netherlands Biotechnological Society.

  • Van Wezel, A. L., Van der Velden-De Groot, C. A. M., De Haan, H. H., Van den Heuvel, N. andSchasfoort, R. 1984. Large scale cell cultivation for the production of cellular biologicals and virus vaccines.In ESACT-IABS Meeting on Production and Exploitation of Existing and New Ánimal Cell Substrates, Dev. Biol. Stand. — S. Karger, Basel (in press).

  • Wide, L. andGemzell, C. A. 1960. An immunological pregnancy test. — Acta Endocrinol.35: 261–267.

    CAS  PubMed  Google Scholar 

  • Zimmermann, U. 1983. Electrofusion of cells: principles and industrial potential. — Trends Biotechnol.1: 149–155.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schönherr, O.T., Houwink, E.H. Antibody engineering, a strategy for the development of monoclonal antibodies. Antonie van Leeuwenhoek 50, 597–623 (1984). https://doi.org/10.1007/BF02386229

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02386229

Keywords

Navigation