Skip to main content

Human—Human Hybridoma Technology

Five Years of Technical Improvements, and Its Application in Cancer Biology

  • Chapter
Human Hybridomas and Monoclonal Antibodies

Abstract

Cloning and immortalization of antibody-producing human B lymphocytes are required to establish monoclonal cell lines that secrete human immunoglobulin of predefined specificity. Such cultures may be obtained either (1) by transformation of normal B lymphocytes, e.g., by virus, or (2) by somatic cell hybridization of normal B lymphocytes with malignant cells, resulting in cell hybrids that have preserved the secretion of specific antibody of the B lymphocyte and the growth properties of the malignant cells. The former method has been used almost exclusively with Epstein—Barr virus (EBV) as the transforming agent, and some human monoclonal antibodies with interesting specificity have been obtained by this method (Steinitz et al., 1979; Zurawski et al., 1978; Irie et al.,1982; Watson et al., 1983; Rosen et al.,1983).

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

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

    PubMed  CAS  Google Scholar 

  • Antel, J., Oger, J. J.-F., Iackevicius, S., Kuo, H. H., and Arnason, B. G. W., 1982, Modulation of T-lymphocyte differentiation antigens: Potential relevance for multiple sclerosis, Proc. Natl. Acad. Sci. USA 79: 3330–3334.

    Article  PubMed  CAS  Google Scholar 

  • Brodin, T., Olsson, L., and Sjögren, H. 0., 1983, Cloning of human myeloma/hybridoma and lymphoma cell lines by enriched human monocytes as feeder layer, J. Immunol. Meth. 61: 1–7.

    Article  Google Scholar 

  • Bumol, T. F., and Reisfeld, R. A., 1982, Unique glycoprotein–proteoglycon complex defined by monoclonal antibody on human melanoma cells, Proc. Natl. Acad. Sci. USA 79: 1245–1249.

    Article  PubMed  CAS  Google Scholar 

  • Cote, R. J., Morrissey, D. M., Houghton, A. N., Beattie, E. J., Oettgen, H. F., and Old, L. J., 1983, Generation of human monoclonal antibodies reactive with cellular antigens, Proc. Natl. Acad. Sci. USA 80: 2026–2030.

    Article  PubMed  CAS  Google Scholar 

  • Croce, C. A., Linnenbach, A., Hall, W., Steplewski, Z., and Koprowski, H., 1980, Production of human hybridomas secreting antibody to measles virus, Nature 228: 486–488.

    Google Scholar 

  • Doerfler, W., 1983, DNA methylation and gene activity, Annu. Rev. Biochem. 52: 93–124.

    Article  PubMed  CAS  Google Scholar 

  • Feizi, T., 1984, Monoclonal antibodies reveal saccharine structures of glycoproteins and glycolipids as differentiation and tumor associated antigens, in: Genes and Antigens in Cancer Cells—The Monoclonal Antibody Approach ( G. Riethmuller, H. Koprowski, S. von Kleist, and K. Munk, eds.), Karger, Basel, pp. 51–63.

    Google Scholar 

  • Frost, P., and Kerbel, R. S., 1983, On a possible epigenetic mechanism(s) of tumor cell heterogeneity, Cancer Metastasis Rev. 2: 375–378.

    Article  PubMed  CAS  Google Scholar 

  • Frost, P., Liteplo, R. G., Donaghue, T. P., and Kerbel, R. S., 1984, Selection of strongly immunogenic “turn-” variants from tumors at high frequency using 5-azacytidine, J. Exp. Med. 159: 1491–1501.

    Article  PubMed  CAS  Google Scholar 

  • Gallagher, R., Collins, S., Trufillo, J., McGredie, K., Ahearn, M., Tsai, S., Metzgar, R., Anlakh, G., Ting, R., Ruscetti, F., and Gallo, R. C., 1979, Characterization of the continuous differentiating myeloid cell line (HL-60) from a patient with acute promyelocytic leukemia, Blood 54: 713–733.

    PubMed  CAS  Google Scholar 

  • Ginsburg, V., Fredman, P., and Magnani, J., 1984, Cancer associated carbohydrate antigens detected by monoclonal antibodies, in: Genes and Antigens in Cancer Cells—The Monoclonal Antibody Approach ( G. Riethmuller, H. Koprowski, S. von Kleist, and K. Munk, eds.), Karger, Basel, pp. 51–63.

    Google Scholar 

  • Hakomori, S., and Kannagi, R., 1983, Glycosphingolipids as tumor-associated and differentiation markers, J. Natl. Cancer Inst. 71: 231–251.

    PubMed  CAS  Google Scholar 

  • Hansson, G. C., Karlsson, K.-A., Larson, G., McKibbin, J. M., Blaszcyzyk, M., Herlyn, M., Steplewsky, Z., and Koprowski, H., 1983, Mouse monoclonal antibodies against human cancer cell lines with specificities for blood group and related antigens. Characterization by antibody binding to glycosphingolipids in a chromatogram binding assay,/ Biol. Chem. 258: 4091–4097.

    CAS  Google Scholar 

  • Hawkes, R., Niday, E., and Gordon, J., 1982, A dot-immunobinding assay for monoclonal and other antibodies, Anal. Biochem. 1. 19: 142–147.

    Google Scholar 

  • Hellström, K. E., Hellström, I., Brown, J. P., Larson, S. M., Nepom, G. T., and Carosquillo, J. A., 1984, Three human melanoma-associated antigens and their possible clinical applications, in: Genes and Antigens in Cancer Cells—The Monoclonal Antibody Approach ( G. Riethmuller, H. Koprowski, S. von Kleist, and K. Munk, eds.), Karger, Basel, pp. 121–131.

    Google Scholar 

  • Heppner, G. H., 1984, Tumor heterogeneity, Cancer Res. 44: 2259–2265.

    PubMed  CAS  Google Scholar 

  • Holliday, R., and Pough, J. E., 1975, DNA modification mechanisms and gene activity during development, Science 187: 226–232.

    Article  PubMed  CAS  Google Scholar 

  • Houghton, A. N., Brooks, H., Cote, R. J., Taormina, M. C., Oettgen, H. F., and Old, L. J., 1983, Detection of cell surface and intracellular antigens by human monoclonal antibodies: Hybrid cell lines derived from lymphocytes of patients with malignant melanoma, J. Exp. Med. 158: 53–65.

    Article  PubMed  CAS  Google Scholar 

  • Irie, R. F., Sze, L. L., and Saxton, R. E., 1982, Human antibody to OFA-I, a tumor antigen, produced in vitro by Epstein–Barr virus-transformed human B-lymphoid cell lines, Proc. Natl. Acad. Sci. USA 79: 5666–5670.

    Article  PubMed  CAS  Google Scholar 

  • Kaplan, H. S., Olsson, L., and Raubitschek, A., 1982, Monoclonal human antibodies: A recent development with wide-ranging clinical potential, in: Monoclonal Antibodies in Clinical Medicine ( A. J. McMichael and J. W. Fabre, eds.), Academic Press, London, pp. 17–35.

    Google Scholar 

  • Kozbor, D., and Roder, J. C., 1983, The production of human monoclonal antibodies from human lymphocytes, Immunol. Today 4: 72–79.

    Article  CAS  Google Scholar 

  • Lane, D., and Koprowski, H., 1982, Molecular recognition and the future of monoclonal antibodies, Nature 296: 200–201.

    Article  PubMed  CAS  Google Scholar 

  • Mitchell, M. S., and Oettgen, A. F. (eds.), 1983, Hybridomas in Cancer Diagnosis and Treatment, Raven Press, New York.

    Google Scholar 

  • Nilsson, K., Bennich, H., Johansson, G. S. O., and Pontén, J., 1970, Established immunoglobulin producing myeloma (IgE) and lymphoblastoid (IgG) cell lines from an IgE myeloma patient, Clin. Exp. Immunol. 7: 477–489.

    PubMed  CAS  Google Scholar 

  • Old, L. J., Stockert, E., Bogse, E. A., and Kim, J. H., 1968, Antigenic modulation. Loss of TL antigen from cells exposed to TL antibody—Study of the phenomenon in vitro, J. Exp. Med. 127: 523–529.

    Article  PubMed  CAS  Google Scholar 

  • Olsson, L., 1983, Phenotypic diversity in leukemia cell populations, Cancer Metastasis Rev. 2: 153163.

    Google Scholar 

  • Olsson, L., 1984, Human monoclonal antibodies: Methods of production and some aspects of their application in oncology, Med. Oncol. Tumor Pharmacother. 4: 235–246.

    Google Scholar 

  • Olsson, L., Andreasen, R. B., Ost, Ake, Christensen, B., and Biberfeld, P., 1984, Antibody-producing human—human hybridomas II. Derivation and characterization of an antibody specific for human leukemia cells, J. Exp. Med. 159: 537–551.

    Article  PubMed  CAS  Google Scholar 

  • Olsson, L., Due, C., Diamant, M., 1985, Treatment of human cell lines with 5-azacytidine may result in profound alterations in clonogenicity and growth rate. J. Cell. Biol. 100: 508–513.

    Article  PubMed  CAS  Google Scholar 

  • Olsson, L., and Forchhammer, J., 1984, Induction of the metastatic phenotype in a mouse tumor model by 5-azacytidine and characterization of an antigen associated with metastatic activity, Proc. Natl. Acad. Sci. USA 81: 3389–3393.

    Article  PubMed  CAS  Google Scholar 

  • Olsson, L., and Kaplan, H. S., 1980, Human—human hybridomas producing monoclonal antibodies of predefined antigenic specificity, Proc. Natl. Acad. Sci. USA 77: 5429–5431.

    Article  PubMed  CAS  Google Scholar 

  • Olsson, L., and Kaplan, H. S., 1983, Human—human monoclonal antibody-producing hybridomas. Technical aspects, Meth. Enzymol. 92: 3–16.

    Article  PubMed  CAS  Google Scholar 

  • Olsson, L., Kronstr¢m, H., Cambon-de-Mouzon, A., Honsik, C. J., Brodin, T., and Jacobsen, B., 1983, Antibody-producing human—human hybridomas. I. Technical aspects, J. Immunol. Meth. 61: 17–32.

    CAS  Google Scholar 

  • Pettijohn, D., Henzl, M., and Price, C., 1984, Nuclear proteins which become part of the mitotic apparatus: A role in nuclear assembly?]. Cell Sci.,in press.

    Google Scholar 

  • Razin, A., and Riggs, A. D., 1980, DNA methylation and gene regulation, Science 210:604–610. Reading, C. L., 1982, Theory and methods for immunization in culture and monoclonal antibody production, J. Immunol. Meth. 53: 261–291.

    Google Scholar 

  • Riggs, A. D., and Jones, P. A., 1983, 5-Methylcytosine, gene regulation and cancer, Adv. Cancer Res. 40: 1–30.

    Google Scholar 

  • Ritz, J., Pesando, J. M., Notis-McConarty, J., and Schlossman, S. F., 1980, Modulation of human acute lymphoblastic leukemia antigen induced by monoclonal antibody in vitro, J. Immunol. 125: 1506–1514.

    PubMed  CAS  Google Scholar 

  • Rosen, A., and Klein, G., 1983, UV-light-induced immunoglobulin heavy-chain class switch in a human lymphoblastoid cell line, Nature 306: 189–191.

    Article  PubMed  CAS  Google Scholar 

  • Rosen, A., Persson, K., and Klein, G., 1983, Human monoclonal antibodies to a genus-specific chlamydial antigen produced by EBV-transformed B-cells, J. Immunol. 130: 2899–2902.

    PubMed  CAS  Google Scholar 

  • Schlom, J., Wunderlich, D., and Teramoto, Y. A., 1980, Generation of human monoclonal antibodies reactive with human mammary carcinoma cells, Proc. Natl. Acad. Sci. USA 77: 6841–6845.

    Article  PubMed  CAS  Google Scholar 

  • Sikora, K., Alderson, J., Philips, J., and Watson, J. V., 1982, Human hybridomas from malignant gliomas, Lancet I:11–14.

    Google Scholar 

  • Steinitz, M., Klein, G., Koskimies, S., and Kakela, 0., 1979, EB virus-induced cell lines producing specific antibody, Nature 269: 420–422.

    Article  Google Scholar 

  • Van Ness, J., Laemmli, U. K., and Pettijohn, D. E., 1984, Immunization in vitro and production of monoclonal antibodies specific to insoluble and weakly immunogenic proteins, Proc. Natl. Acad. Sci. USA 81: 7897–7901.

    Article  PubMed  Google Scholar 

  • Watson, D. B., Burns, G. F., and Makay, I. R., 1983, In vitro growth of B-lymphocytes infiltrating human melanoma tissue by transformation with EBV: Evidence for secretion of anti-melanoma antibodies by some transformed cells, J. Immunol. 130: 2442–2447.

    CAS  Google Scholar 

  • Zurawski, V. R., Haber, E., and Black, P. M., 1978, Production of antibody to tetanus toxoid by continuous human lymphoblastoid cell lines, Science 119: 1439–1441.

    Article  Google Scholar 

  • Acton, R. T., Barstad, P. A., and Zuerner, R. K., 1979, Propagation and scaling-up of suspension culture, Meth. Enzymol. LVIII: 211–221.

    Google Scholar 

  • Chang, T. H., Steplewski, Z., and Koprowski, H., 1980, Production of monoclonal antibodies in serum-free medium, J. Immunol. Meth. 39: 369–375.

    Article  CAS  Google Scholar 

  • Erhlich, K. C., Stewart E., and Klein, E., 1978, Artificial capillary perfusion cell culture: Metabolic studies, In Vitro 14: 443–450.

    Article  Google Scholar 

  • Fazekas de St. Groth, S., 1983, Automated production of monoclonal antibodies in a cytostat, J. Immunol. Meth. 57: 121–136.

    Article  Google Scholar 

  • Feder, J., and Tolbert, W. R., 1983, Large scale cultivation of mammalian cells, Sci. Am. 248: 3643.

    Google Scholar 

  • Finter, N. B., and Fantes, K. H., 1980, The purity and safety of interferons prepared for clinical use: The case for lymphoblastoid interferon, In: Interferon II, I. Gessor, ed., Academic Press, New York, pp. 65–80.

    Google Scholar 

  • Girard, H. C., Sutcu, M., Erden, H., and Gurhan, I., 1980, Monolayer cultures of animal cells with the cyrogen equipped with tubes, Biotechnol. Bioeng. 22: 477–493.

    Article  Google Scholar 

  • Glacken, M. W., Fleischaker, R. J., and Sinskey, A. J., 1983, Mammalian cell culture: Engineering principles and scale-up, Trends Biotechnol. 1: 102–108.

    Article  CAS  Google Scholar 

  • Himmelfarb, P., Thayer, P. S., and Martin, H. E., 1969, Spin filter culture: The propagation of mammalian cells in suspension, Science 164: 555–557.

    Article  PubMed  CAS  Google Scholar 

  • Hopkinson, J., 1982, Hollow Fiber Cell Culture: A Sleeping Giant Awakening, Amicon Literature, Amicon Corp., Lexington, Massachusetts.

    Google Scholar 

  • Iscove, N. N., and Melchers, 1978, Complete replacement of serum by albumin, transferrin, and soybean lipid in cultures of lipopolysaccharide-reactive B lymphocytes, J. Exp. Med. 147: 923933.

    Google Scholar 

  • Jarvis, A. P., and Grdina, T. A., 1983, Production of biologicals from microencapsulated living cells, Bio Techniques 1: 24–27.

    Google Scholar 

  • Kawamoto, T., Sato, J. D., Lo, A., McClure, D. B., and Sato, G. H., 1983, Development of a serum-free medium for growth of NS-1 mouse myeloma cells and its application to the isolation of NS-1 hybridomas, Anal. Biochem. 130: 445–453.

    Article  PubMed  CAS  Google Scholar 

  • Knazek, R. A., Gullino, P. M., Kohler, P. O., and Dedrick, R. L., 1972, Cell culture on artificial capillaries: An approach to tissue culture in vitro, Science 178: 65–67.

    Article  PubMed  CAS  Google Scholar 

  • Kruse, P. F., Jr., and Patterson, M. K. Jr., (eds.), Tissue Culture, Methods and Applications,Volume XXVII, Academic Press, New York, pp. 283–363.

    Google Scholar 

  • Lewis, C., Tolbert, W. R., and Feder, J., 1984, Large scale perfusion culture system for production of monoclonal antibodies, presented at Hybridoma Conference, San Diego, California.

    Google Scholar 

  • Lim, F., and Sun, A., 1980, Microencapsulated islets of bioartificial endocrine pancreas, Science 210: 908–910.

    Article  PubMed  CAS  Google Scholar 

  • Littlefield, S. G., Gilligan, K. J., and Jarvis, A. P., 1983, Growth and monoclonal antibody production from rat x mouse hybridomas: A comparison of microcapsule culture with conventional suspension culture, presented at Hybridoma Conference, San Diego, California.

    Google Scholar 

  • Litwin, J., 1973, Titanium disks, In: Tissue Culture Methods and Applications, P. F. Kruse, Jr., and M. K. Patterson, Jr., eds., Academic Press, New York, Chapter 5.

    Google Scholar 

  • Lydersen, B. K., Pugh, G. G., Duncan, E. C., Overman, K. T., Johnson, D. M., and Sharma, B. P., 1983, Novel ceramic material for large scale cell culture, presented at Tissue Culture Association, 34th Annual Meeting, Orlando, Florida, June 12–16.

    Google Scholar 

  • Lynn, J. D., and Acton, R. T., 1975, Design of a large scale mammalian cell suspension culture facility, Biotechnol. Bioeng. XVII: 659–673.

    Article  Google Scholar 

  • McHugh, Y. E., Walthall, B. J., and Steimer, K. S., 1983, Serum-free growth of murine and human lymphoid and hybridoma cell lines, Biotechniques 1: 72–77.

    Google Scholar 

  • McLimans, W. F., 1979, Mass culture of mammalian cells, Meth. Enzymol. LVIII:194–211.

    Article  Google Scholar 

  • Murakami, H., Masui, H., Sato, G. H., Sueoka, N., Chow, T. P., and Kano-Sueoka, T., 1982, Growth of hybridoma cells in serum-free medium: Ethanolamine is an essential component, Proc. Natl. Acad. Sci. USA 79: 1158–1162.

    Article  PubMed  CAS  Google Scholar 

  • Patterson, N. K., Jr., 1976, Perfusion and mass culture systems, Tiss. Culture Assoc. Manual 4: 243–249.

    Article  Google Scholar 

  • Pharmacia, 1981, Microcarrier Cell Culture: Principles and Methods, Pharmacia Fine Chemicals AB, Uppsala, Sweden.

    Google Scholar 

  • Pollard, R., and Khosrovi, B., 1978, Reactor design for fermentation of fragile tissue cells, Process Biochem. 78: 31–37.

    Google Scholar 

  • Quarles, J. M., Morris, N. G., and Leibovitz, A., 1980, Carcinoembryonic antigen production by human colorectal adenocarcinoma cells in matrix-perfusion culture, In Vitro 16: 113–118.

    Article  PubMed  CAS  Google Scholar 

  • Reuveny, S., Mizrahi, A., Kotler, M., and Freeman, A., 1983, Factors affecting cell attachment, spreading and growth on derivatized microcarriers. I. Establishment of working system and effect of the type of the amino-charged groups, Biotechnol. Bioeng. 25: 469–480

    Article  PubMed  CAS  Google Scholar 

  • Reuveny, S., Mizrahi, A., Kotler, M., and Freeman, A., 1983, Introduction of hydrophobic elements, Biotechnol. Bioeng. 25: 2969–2981.

    Article  PubMed  CAS  Google Scholar 

  • Sato, G., Pardee, A. B., and Sirbasku, D. A. (eds.), 1982, Growth of Cells in Hormonally Defined Media, Parts A, B, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.

    Google Scholar 

  • Thayer, P. S., 1973, Spin filter device for suspension cultures, In: Tissue Culture, Methods and Applications, P. F. Kruse, Jr. and M. K. Patterson, Jr., eds., Academic Press, New York, pp. 345–351.

    Google Scholar 

  • Thilly, W. G., Barngrover, D., and Thomas, J. N., 1982, Microcarriers and the problem of high cell density culture, In: From Gene to Protein: Translation into Biotechnology, F. Ahmad, J. Schultz, E. E. Smith, and W. I. Whelan, eds., Academic Press, New York, pp. 75–103.

    Google Scholar 

  • Tolbert, W. R., and Feder, J., 1983, Large scale cell culture technology, Annu. Rep. Fermentation Processes 6: 35–74.

    Google Scholar 

  • Tolbert, W. R., Feder, J., and Kimes, R. C., 1981, Large scale rotating filter perfusion systems for high density growth of mammalian suspension cultures, In Vitro 17: 885–890.

    Article  PubMed  CAS  Google Scholar 

  • Uittenbogaart, C. H., Cantor, Y., and Fahey, J. L., 1983. Growth of human malignant lymphoid cell lines in serum-free medium, In Vitro 19: 67–72.

    Article  PubMed  CAS  Google Scholar 

  • Van Wezel, A. L., and Van der Velden-de Groot, C. A. M., 1978, Large scale cultivation of animal cells in microcarrier culture, Process Biochem. 78: 6–8.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1985 Plenum Press, New York

About this chapter

Cite this chapter

Olsson, L., Brams, P. (1985). Human—Human Hybridoma Technology. In: Engleman, E.G., Foung, S.K.H., Larrick, J.W., Raubitschek, A.A. (eds) Human Hybridomas and Monoclonal Antibodies. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-4949-5_13

Download citation

  • DOI: https://doi.org/10.1007/978-1-4684-4949-5_13

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-4951-8

  • Online ISBN: 978-1-4684-4949-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics