Abstract
Several years before the application of Köhler and Milstein’s (1975) hybridoma technology to the production of human monoclonal antibodies, human lymphoid lines producing antibody with defined antigenic specificity were established by Epstein-Barr virus (EBV) “immortalization” (Steinitz et al., 1977). EBV is a lymphotropic herpes virus, which transforms normal B lymphocytes and makes it possible to culture these cells as permanent lines. Rosen et al. (1977) demonstrated that direct infection of purified human blood lymphocytes with EBV in vitro induced polyclonal secretion of immunoglobulins. Culture supernatants assayed by immunoassay contained a heterogeneous assortment of immunoglobulin isotypes and antibodies specific for various randomly selected antigens. It became obvious, then, that if monospecific B cells could be transformed in vitro into continuous cell lines by EBV and if these “immortalized” cells could be triggered to produce antibodies, permanent lines of B lymphocytes might be established that were capable of producing specific monoclonal antibodies against any appropriate antigen.
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References
Atlaw, T., Kozbor, D., and Roder, J. C., 1985, Human monoclonal antibodies against Mycobacterium Leprae, Infect. Immun.,in press.
Boylston, A. W., Gardner, B., Anderson, R. L., and Hughes-Jones, N. C., 1980, Production of human IgM anti-D in tissue culture by EB-virus transformed lymphocytes, Scand. J. Immunol. 12: 355–358.
Chiorazzi, N., Wasserman, R. L., and Kunkel, H. G., 1982, Use of Epstein—Barr virus-transformed B cell lines for the generation of immunoglobulin-producing human B cell hybridomas, J. Exp. Med. 156: 930–935.
Cole, S. P. C., Campling, B. G., Atlaw, T., Kozbor, D., and Roder, J. C., 1984a, Human monoclonal antibodies, Mol. Cell. Biol., 62: 109–120.
Cole, S. P. C., Campling, B. G., Louwman, I. H., Kozbor, D., and Roder, J. C., 1984b, A strategy for the production of human monoclonal antibodies reactive with lung tumour cell lines, Cancer Res., 44: 2750–2753.
Crawford, D. H., Barlow, M.J., Harrison, J. F., Winger, L., and Huehns, E. R., 1983a, Production
Crawford, D. H., Callard, R. E., Muggeridge, M. I., Mitchell, D. M., Zanders, E. D., and Beverley, P. C. L., 1983b, Production of human monoclonal antibody to X31 influenza virus nucleoprotein, J. Gen. Virol. 64: 697–700.
Crawford, D. H., Heuhns, E. R., and Epstein, M. A., 1983c, Therapeutic use of human monoclonal antibodies, Lancet i:1040 (letter).
Croce, C. M., Linnenbach, A., Hall, W., Steplewski, Z., and Koprowski, H., 1980, Production of human hybridomas secreting antibodies to measles virus, Nature 288: 488.
Dillman, R. O., Shawler, D. L., Sobol, R. E., Collins, H. A., Beauregard, J. C., Wormsley, S. B., and Royston, I., 1982, Murine monoclonal antibody therapy in two patients with chronic lymphocytic leukemia, Blood 59: 1036–1045.
Irie, R. F., Sze, L. L., and Saxton, R. E., 1982, Human antibody to OFA-1, a tumor antigen produced in vitro by Epstein-Barr virus-transformed human B-lymphoid cell lines, Proc. Natl. Acad. Sci. USA 79: 5666–5670.
Kamo, I., Furukawa, S., Tada, A., Mano, Y., Iwasaki, Y., and Furuse, T., 1982, Monoclonal antibody to acetylcholine receptor: Cell line established from thymus of patient with myasthenia gravis, Science 215: 995–997.
Köhler, G., and Milstein, C., 1975, Continuous cultures of fused cells secreting antibody of predefined specificity, Nature 256: 495–497.
Koskimies, S., 1979, A human lymphoblastoid cell line producing specific antibody against Rh-antigen D, Scand. J. Immunol. 10: 371 (abstract).
Kozbor, D., and Roder, J. C., 1981, Requirements for the establishment of high titered human monoclonal antibodies against tetanus toxoid using the Epstein—Barr virus technique, J. Immunol. 127: 1275–1280.
Kozbor, D., and Roder, J. C., 1983, Monoclonal antibodies produced by human lymphocytes, Immunol. Today 4: 72–79.
Kozbor, D., and Roder, J., 1984, In vitro stimulated lymphocytes as a source of human hybridomas, Eur. J. Immunol., 14: 23–27.
Kozbor, D., Steinitz, M., Klein, G., Koskimies, S., and Makela, O., 1979, Establishment of anti-TNP antibody-producing human lymphoid lines by preselection for hapten binding followed by EBV transformation, Scand. J. Immunol. 10: 187–194.
Kozbor, D., Roder, J. C., Chang, T. H., Steplewski, Z., and Koprowski, H., 1982a, Human anti-tetanus toxoid monoclonal antibody secreted by EBV-transformed human B cells fused with a murine myeloma, Hybridoma 1: 323–328.
Kozbor, D., Lagarde, A., and Roder, J. C., 1982b, Human hybridomas constructed with antigen-specific, EBV-transformed cell lines, Proc. Natl. Acad. Sci. USA 79: 6651–6655.
Kozbor, D., Dexter, D., and Roder, J. C., 1983, A comparative analysis of the phenotypic characteristics of available fusion partners for the construction of human hybridomas, Hybridoma 2: 7–16.
Kozbor, D., Tripputi, P., Roder, J. C., and Croce, C. M., 1984, A human hybrid myeloma is an efficient fusion partner that enhances monoclonal antibody production, J. Immunol. 133: 3001–3005.
Laskov, R., Kim, J. K., and Asofsky, R., 1979, Induction of amplified synthesis and secretion of IgM by fusion of murine B lymphoma with myeloma cells, Proc. Natl. Acad. Sci. USA 76: 915–919.
Levy, R., and Dilley, J., 1978, Rescue of immunoglobulin secretion from human neoplastic lymphoid cells by somatic cell hybridization, Proc. Natl. Acad. Sci. USA 75: 2411–2415.
McGarry, R., Cole, S. P. C., and Roder, J., 1985, Human hybridomas from patients with peripheral demyelination react with myelin-associated glycoprotein, manuscript in preparation.
Miller, G., and Lipman, M., 1973, Release of infectious Epstein-Barr virus by transformed marmoset leukocytes, Proc. Natl. Acad. Sci. USA 70: 190–194.
Miller, R. A., and Levy, R., 1981, Response of cutaneous T-cell lymphoma to therapy with hybridoma monoclonal antibody, Lancet 2: 226–230.
Miller, R. A., Maloney, D. G., McKillop, J., and Levy, R., 1981, In vivo effects of murine hybridoma monoclonal antibody in a patient with T-cell leukemia, Blood 58: 78–86.
Miller, R. A., Maloney, D. G., Warnke, R., and Levy, R., 1982, Treatment of B-cell lymphoma with monoclonal anti-idiotype antibody, N. Engl. J. Med. 306: 517–522.
Milstein, C., and Cuello, A. C., 1983, Hybrid hybridomas and their use in immunohistochemistry, Nature 305: 537–540.
Miyoshi, I., Kubonishi, E., Yoshimoto, S., Akagi, T., Ohtsuki, Y., Shiraishr, Y., Nagata, K., and Hinuma, Y., 1981, Type C virus particles in a cord T-cell line derived by co-cultivating normal human cord leukocytes and leukemia T cells, Nature 294: 770–771.
Nadler, L. M., Stashenko, P., Hardy, R., Kaplan, W. D., Button, L. N., Kufe, D. W., Atman, K. H., and Schlossman, S. F., 1980, Serotherapy of a patient with a monoclonal antibody directed against a human lymphoma-associated antigen, Cancer Res. 40: 3147–3154.
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.
Poiesz, B. J., Ruscetti, F. W., Gazdar, A. F., Bunn, P. A., Minna, J. D., and Gallo, R. C., 1980, Detection and isolation of type C retrovirus particles from fresh and ‘ultured lymphocytes of a patient with cutaneous T-cell lymphoma, Proc. Natl. Acad. Sci. USA 77: 7415–7419.
Ritz, J., Pesando, J. M., Sallan, S. E., Clavell, L. A., Notis-McConarty, J., Rosenthal, P., and Schlossman, S. F., 1981, Serotherapy of acute lymphoblastic leukemia with monoclonal antibody, Blood 58: 141–151.
Rosen, A., and Klein, G., 1983, UV light-induced immunoglobulin heavy-chain class switch in a human lymphoblastoid cell line, Nature 306: 189–190.
Rosen, A., Britton, S., Gergely, P., Jondal, M., and Klein, G., 1977, Polyclonal Ig production after Epstein—Barr virus infection of human lymphocytes, Nature 267: 52–54.
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.
Schulman, M., Wilde, C. D., and Kohler, G., 1978, A better cell line for making hybridomas secreting specific antibodies, Nature 276: 269–270.
Sears, H. F., Atkinson, B., Herlyn, D., Ernst, C., Matteis, J„ Steplewski, Z., and Koprowski, H., 1982, Phase I clinical trial of monoclonal antibody in treatment of gastrointestinal tumours, Lancet i:762–765.
Seigneurin, J. M., Desgranges, C., Seigneurin, D., Paire, J., Renversez, J. C., Jacquemont, B., and Micouin, C., 1983, Herpes simplex virus glycoprotein D: Human monoclonal antibody produced by bone marrow cell line, Science 221: 173–175.
Sikora, K., Alderson, T., Phillips, J., and Watson, J. V., 1982, Human hybridomas from malignant gliomas, Lancet i:11–14.
Sikora, K., Alderson, T., Ellis, J., Phillips, J., and Watson, J., 1983, Human hybridomas from patients with malignant disease, Br. J. Cancer 47: 135–145.
Steinitz, M., and Tamir, S., 1982, Human monoclonal autoimmune antibody produced in vitro: Rheumatoid factor generated by Epstein-Barr virus-transformed cell line, Eur. J. Immunol. 12: 126–133.
Steinitz, M., Klein, G., Koskimies, S., and Makela, O., 1977, EB virus-induced B lymphocyte cell lines producing specific antibody, Nature 269: 420–422.
Steinitz, M., Seppala, F., Eichman, K., and Klein, G., 1979, Establishment of a human lymphoblastoid cell line with the specific antibody production against group A streptococcal carbohydrate, Immunobiology 156: 41–47.
Steinitz, M., Izak, G., Cohen, S., Ehrenfeld, M., and Flechner, I., 1980, Continuous production of monoclonal rheumatoid factor by EBV-transformed lymphocytes, Nature 287: 443–445.
Stevens, R. H., Macy, E., Morrow, C., and Saxon, A., 1979, Characterization of a circulating subpopulation of spontaneous anti-tetanus toxoid antibody producing B cells following in vivo booster immunization, J. Immunol. 122: 2498–2504.
Sullivan, J. L., Byron, K. S., Brewster, F. F., and Purtilo, D., 1980, Deficient natural killer cell activity in X-linked lymphoproliferative syndrome, Science 210: 543–545.
Tsuchiya, S., Yokoyama, S., Yoshie, O., and Ono, Y., 1980, Production of diptheria antitoxin antibody in Epstein-Barr virus-induced lymphoblastoid cell lines, J. Immunol. 124: 1970–1976.
Walker, S. M., Meinke, G. C., and Weigle, W. O., 1977, Cell separation on antigen-coated columns. Elimination of high rate antibody-forming cells and immunological memory cells, J. Exp. Med. 146: 445–446.
Watson, D. B., Burns, G. F., and MacKay, 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.
Watson, J. V., Alderson, T., Sikora, K., and Phillips, J., 1983, Subcutaneous culture chamber for continuous infusion of monoclonal antibodies, Lancet i:99–100.
Weiss, R. A., 1982, Hybridomas produce viruses as well as antibodies, Immunol. Today 3: 292–294.
Winger, L., Winger, C., Shastry, P., Russell, A., and Longenecker, M., 1983, Efficient generation in vitro, from human peripheral blood cells, of monoclonal Epstein-Barr virus transformants producing specific antibody to a variety of antigens without prior deliberate immunization, Proc. Natl. Acad. Sci. USA 80: 4484–4488.
Yoshie, O., and Ono, Y., 1980, Anti-phosphorylcholine antibody producing cells in human lymphoblastoid cell lines established by transformation with Epstein-Barr virus, Gell. Immunol. 56: 305–315.
Zurawski, V. R., Jr., Haber, E., and Black, P. M., 1978a, Production of antibody to tetanus toxoid by continuous human lymphoblastoid cell lines, Science 199: 1439–1441.
Zurawski, V. R., Jr., Spedden, S. E., Black, P., and Haber, E., 1978b, Clones of human lymphoblastoid cell lines producing antibody to tetanus toxoid, Gurr. Top. Microbiol. Immunol. 81: 152–155.
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Roder, J.C., Cole, S.P.C., Atlaw, T., Campling, B.G., McGarry, R.C., Kozbor, D. (1985). The Epstein—Barr Virus-Hybridoma Technique. 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_4
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DOI: https://doi.org/10.1007/978-1-4684-4949-5_4
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