Abstract
To be suitable for fusion, myeloma and other tumor cells must fulfil the following four conditions:
-
1.
They may no longer synthesize intact antibody or immunoglobulin light or heavy chains themselves.
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2.
They must possess an enzyme defect, to allow their selective elimination after the fusion.
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3.
They should have good fusion properties, so that the number of hybridomas produced is as large as possible.
-
4.
Their molecular properties should induce a high rate of MAB synthesis in the hybridoma.
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References
Alt FW, Kellems RE, Bertino JR, Schimke RT (1978) Selective multiplication of dihydrofalate reductase genes in methotrexate-resistant variants of cultured murine cells. J Biol Chem 253:1357–70d
Baker RM, Brunette DM, Mankovitz R, Thompson LH, Whitmore GF, Siminovitch L, Till JE (1974) Quabain-resistant mutants of mouse and hamster cells in culture. Cell 1:9–21
Besnard C, Monthioux E, Jami J (1987) Selection against expression of the Escherichia coli gene gpt in hprt +mouse teratocarcinoma and hybrid cells. Mol Cell Biol 7:4139–4141
Chan RS, Creagen RP, Reardon MP (1978) Adenosine kinase as a new selective marker in somatic cell genetics: isolation of adenosine kinase-deficient mouse cell lines and human-mouse hybrid cell lines containing adenosine kinase. Somatic Cell Genet 4:1–12
Crane IJ, Leung H, Parti S, Meager A (1985) Ricin-resistant human T-cell hybridomas producing interferon gamma. J Immunol Methods 77:207–218
D’Urso M, Mareni C, Toniolo D, Piscopo M, Schlessinger D, Luzzatto L (1983) Regulation of glucose 6-phosphate dehydrogenase expression in CHO-human fibroblast somatic cell hybrids. Somatic Cell Genet 9:429443
Edwards PAW, Smith CM, Munro Neville A, O’Hare MJ (1982) A human-human hybridoma system based on a fast-growing mutant of the ARH-77 plasma cell leukemia-derived cell line. Eur J Immunol 12:641–648
Engleman EG, Foung SKH, Grumet FC, Raubitschek AR, Larrick JW (1985) Humanmurine hybridoma as a fusion partner and its products. Eur Pat Appl EP 148644 A2, 17 Jul 1985, 41pp.
Evans HJ, Vijayalaxmi (1981) Induction of 8-azaguanine resistance and sister chromatid exchange in human lymphocytes exposed to mitomycin C and X rays in vitro. Nature 292:601–605
Fehlner PF, Bencsath A, Lam T, King TP (1987) The photodecomposition of aminopterin. J Immunol Meth 101:141–145
Foung SKH, Saski DT, Grumet FC, Engleman EG (1982) Production of functional human T-T hybridomas in selection medium lacking aminopterin and thymidine. Proc Natl Acad Sci USA 79:7484–7488
Foung SK, Perkins S, Raubitschek A, Larrick J, Lizak G, Fishwild D, Engleman EG, Grumet FC (1984) Rescue of human monoclonal antibody production from an EBV-transformed B cell line by fusion to a human-mouse hybridoma. J Immunol Methods 70:83–90
Haskard DO, Archer JR (1984) The production of human monoclonal autoantibodies from patients with rheumatoid arthritis by the EBV-hybridoma technique. J Immunol Methods 74:361–367
Hayashi J, Tagashira Y, Higashida H, Hirai S, Yoshida MC, Sekiguchi T (1984) Isolation and characterization of intraspecific cybrids. Effect of mitochondrial DNA on their cellular properties. Exp Cell Res 154:357–366
Hayashi J, Tagashira Y, Watanabe T, Sekiguchi T (1983) Effect of mitochondrial DNA composition on the cellular properties of interspecific hybrid cells. Exp Cell Res 148:258–264
Hayashi J, Tagashira Y, Yoshida MC (1985) Absence of extensive recombination between inter- and intraspecies mitochondrial DNA in mammalian cells. Exp Cell Res 160:387–395
Hirschhorn R, Ellenbogen A, Martiniuk F (1985) An approach to a selection system for adenosine-deaminse-positive (ADA+) cells and detection of rat ADA+ “revertans”. J Cell Physiol 123:277–282
Horenstein AL, Glait HM, Koss A (1987) An improved selection procedure for the rescue of hybridomas. A comparative study of methotrexate versus aminopterin. J Immunol Methods 98:145–149
Howell N (1983) Origin, cellular expression, and cybrid transmission of mitochondrial CAP-R, PYR-IND, and OLI-R mutant phenotypes. Somatic Cell Genet 9:1–24
Howell N, Huang P, Kelliher K, Ryan ML (1983) Mitochondrial genetics of mammalian cells: a mouse antimycin-resistant mutant with a probable alteration of cytochrome b. Somatic Cell Genet 9:143–163
Howell N, Huang P, Kolodner RD (1984) Origin, transmission, and segregation of mitochondrial DNA dimers in mouse hybrid and cybrid cell lines. Somatic Cell Mol Genet 10:259–274
Hulette CM, Effros RB, Dillard LC, Walford RL (1985) Production of a human monoclonal antibody to HLA by human-human hybridoma technology. A preliminary report. Am J Pathol 121:10–14
Hundhausen T (1990) Untersuchungen zur Herstellung humaner T-Lymphozytenhybridome. Inauguraldiss, Kiel
Ichimori Y, Harada K, Hitosumachi S, Tsukamoto K (1987) Establishment of hybridoma secreting human monoclonal antibody against hepatitis B virus surface antigen. Biochem Biophys Res Commun 142:805–812
Kaplan HS, Teng NNH, Lam KS, Calvo-Riera F (1986) Methods and cell lines for immortalization and monoclonal antibody production by antigen-stimulated B-lymphocytes. U.S US 4574116 A, 4 Mar 1986, 6pp.
Kennett RH (1979) Cell fusion. In: Colowick SP, Kaplan NO (eds) Methods in enzymology, vol 58. Academic Press, New York, pp 345–359
Koolwijk P, Rozemuller E, Stad RK, De Lau WBM, Bast BJEG (1988) Enrichment and selection of hybrid hybridomas by Percoll density gradient centrifugation and fluorescent-activated cell sorting. Hybridoma 7:217–225
Kozbor D, Lagarde AE, Roder JC (1982) Human hybridomas with antigenspecific Epstein-Barr virus-transformed cell lines. Proc Natl Acad Sci USA 79:6651–6655
Kozbor D, Roder JC, Chang TH, Steplewski Z, Koprowski H (1982) Human anti-tetanus toxoid monoclonal antibody secreted by EBV-transformed human B cells fused with murine myeloma. Hybridoma 1:323–328
Kusano T, Long C, Green M (1971) A new reduced human-mouse somatic cell hybrid containing human gene for adenine phosphoribosyltransferase. Proc Natl Acad Sci USA 68:82–86
Littlefield JW (1964) Selection of hybrids from matings of fibroblasts in vitro and their presumed recombinants. Science 145:709–710
Paul J (1980) Zell- und Gewebekulturen. De Gruyter, Berlin
Platsoucas CD, Calvelli TA, Kunicka JA (1987) A new method for the development of human T-T cell hybrids without the use of HAT medium. Hybridoma 6:589–603
Posner MR, Elboim H, Santos D (1987) The construction and use of a human-mouse myeloma analogue suitable for the routine production of hybridomas secreting human monoclonal antibodies. Hybridoma 6:611–625
Riera FC, Blam SB, Teng NN, Kaplan HS (1984) Somatic cell hybrid selection with a transferable dominant marker. Somatic Cell Mol Genet 10:123–127
Taggart RT, Samloff IM (1982) Stable antibody-producing murine hybridomas. Science 219:1228–1230
Teng NN, Lam KS, Calvo Riera F, Kaplan HS (1983) Construction and testing of mousehuman heteromyelomas for human monoclonal antibody production. Proc Natl Acad Sci USA 80:7308–7312
Tertov VV, Sayadyan HS, Kalatarov GF, Molotkovxky JG, Bergelson LD, Orekhof AN (1989) Use of lipophilic fluorescent probes for the isolation of hybrid cells in flow cytometry. J Immunol Methods 118:139–143
Tiebout RF, van Boxtel-Oosterhof F, Stricker EA, Zeijlemaker WP (1987) A human hybrid hybridoma. J Immunol 139:3402–3405
Van Snick J, De Plaen E, Boon T (1985) A neomycin-resistant cell line for improved production of monoclonal antibodies to cell surface antigens. Eur J Immunol 15:1151–1153
Wanda PE, Smith JD (1982) A general method for heterokaryon detection using resonance energy transfer and a fluorescence-activated cell sorter. J Histochem Cytochem 30:1297–1300
Wright WE (1984) Toxin-antitoxin selection for isolating somatic cell fusion products between any cell types. Proc Natl Acad Sci USA 81:7822–7826
Zybalski W, Hunter Zbalska E, Ragni G (1962) Genetic studies with human cell lines. Natl Cancer Inst Monogr 7:75–89
References
Kearney JF, Radbruch A, Liesegang B, Rajewski K (1979) A mouse myeloma cell line that has lost immunoglobulin expression but permits the construction of antibody-secreting hybridoma cell lines. J Immunol 123:1548–1558
Köhler G, Howe CS, Milstein C (1976) Fusion between immunoglobulin-secreting and nonsecreting myeloma cell lines. Eur J Immunol 6:292–303
Shulman M, Wilde CG, Köhler G (1978) A better line for making hybridomas secreting specific antibodies. Nature 267:269–271
References
Fazekas de St Groth S, Scheidegger D (1980) Production of monoclonal antibodies: strategy and tactics. J Immunol Methods 35:1–21
French D, Fischberg E, Buhl S, Scharff MD (1986) The production of more useful monoclonal antibodies. I. Modifications of the basic technology. Immunol Today 7:344–346
Kadish JL, Wenc KM (1983) Contamination of polyethylene glycol with aldehydes: implications for hybridoma fusion. Hybridoma 2:87–90
Klebe RJ, Mancuso MG (1981) Chemicals which promote cell hybridization. Somatic Cell Genet 7:473–488
Lane RD, Crissman RS, Ginn S (1986) High efficiency fusion procedure for producing monoclonal antibodies against weak immunogens. In: Langone JJ, Van Vunakis H (eds) Methods in enzymology, vol 121. Immunochemical techniques. Academic Press, New York, pp 183–192
Løvborg U (1982) Monoclonal antibodies. Production and maintenance. Heinemann Medical Books, London
Marusich MF (1988) Efficient hybridoma production using previously frozen splenocytes. J Immunol Methods 114:155–159
Miyahara M, Nakamura H, Hamaguchi Y (1984) Colcemid treatment of myeloma prior to fusion increases the yield of hybridomas myeloma and splenocyte. Biochem Biophys Res Commun 124:903–908
Norwood TH, Zeigler CJ, Martin GM (1976) Dimethyl sulfoxide enhances polyethylene glacol-mediated cell fusion. Somatic Cell Genet 2:263–270
Schneiderman S, Farber JL, Baserga R (1979) A simple method for decreasing toxicity of polyethylene glykol in mammalian cell fusion. Somatic Cell Genet 5:263–269
Shi L, Xu H, Wang D, Dong Z (1987) An improving method to increase fusion rate by using in vivo myeloma cells from solid tumors in BALB/c mice. Chin J Microbiol Immunol 7:324–327
Further Reading
Fox PC, Berenstein EH, Siraganian RP (1980) Enhancing the frequency of antigen-specific hybridomas. Eur J Immunol 11:431–434
Stähli C, Staehelin T, Miggiano V, Schmid J, Häring P (1980) High frequencies of antigenspecific hybridomas: dependence on immunization parameters and prediction by spleen cell analysis. J Immunol Methods 32:297–304
References
Abrams PG, Knost JA, Clarke G, Wilburn S, Oldham RK, Foon KA (1983) Determination of the optimal human cell lines for development of human hybridomas. J Immunol 131:1201–1204
Carroll WJ, Thieleman K, Dilley J, Levy R (1986) Mouse × human heterohybridomas as fusion partners with human B cell tumors. J Immunol Methods 89:61–72
Croce CM, Linnenback A, Hall W, Steplewski Z, Koprowski H (1980) Production of human hybridomas secreting antibodies to measles virus. Nature 288:488–489
Edwards PAW, Smith CM, Neville AM, O’Hare MJ (1982) A human-human hybridoma system based on a fast growing mutant of the ARH-77 plasma cell leukemia-derived line. Eur J Immunol 12:641–648
Foung SHK, Perkins S, Raubitschek A, Larrick J, Lizak G, Fishwild D, Engleman EG, Grumet FC (1984) Rescue of human monoclonal antibody production from an EBV-transformed B cell line by fusion to a human-mouse hybridoma. J Immunol Methods 70:83–90
Glassy MC, Handley HH, Hagiwara H, Royston I (1983) UC-729–6. A Human lymphoblastoid B-cell line useful for generating antibody-secreting human-human hybridomas. Proc Natl Acad Sci USA 80:6327–6331
Heitzmann JG, Cohn M (1983) The WI-L2–729-HF2 human hybridoma system. Mol Biol Med 1:235–243
Ichimori Y, Sasano K, Itoh H, Hitotsumachi S, Kimura Y, Kaneko K, Kida M, Tsukamoto K (1985) Establishment of hybridomas secreting human monoclonal antibodies against tetanus toxin and hepatitis B surface antigen against tetanus toxin and hepatitis B surface antigen. Biochim Biophys Res Commun 129:26–33
Kozbor D, Lagarde AE, Roder JC (1982) Human hybridomas constructed with antigenspecific EBV-transformed lines. Proc Natl Acad Sci USA 79:6651–6655
Kozbor D, Croce CM (1985) Human hybridoma fusion partner for production of human monoclonal antibodies. Eur Patentanmeldung Nr. EP0182467
Larrick JW, Truitt KE, Raubitschek AA, Senyk G, Wang JCN (1983) Characterization of human hybridomas secreting antibodies to tetanus toxoid. Proc Natl Acad Sci USA 80:6367–6380
Larrick JW, Raubitschek AA (1986) Gram-negative bacterial endotoxin blocking monoclonal antibodies and cells producing the same formulations containing the same, and the production of all thereof. Eur Patentanmeldung Nr. EP 0174204
Östberg L, Pursch E (1983) Human × (mouse × human) hybridomas stabely producing human antibodies. Hybridoma 2:361–367
Olsson L, Kaplan HS (1980) Human-human hybridomas producing antibodies of predefined specificity. Proc Natl Acad Sci USA 77:5429–5431
Ritts RE, Ruiz-Argüelles A, Weyl KG, Bradley AL, Weihmeir B, Jacobson D, Strehlo BL (1983) Establishment and characterization of a human non-secretory plasmoid cell line and its hybridization with human B cells. Int J Cancer 31:133–141
Rosen A, Gergely P, Jondal M, Klien G (1977) Polyclonal Ig-production after EBV-infection of human lymphocytes in vitro. Nature 26:52–54
Royston I, Handley H, Seegmiller E, Thompson LF (1984) Immunoglobulin-secreting human hybridomas from a cultured human lymphoblastoid cell line. American Patent No. 4.451.570
Shoenfeld Y, Hsu-Lin SC, Gabriels JE, Silberstein LE, Furie BC, Stollar BD, Schwartz RS (1982) Production of autoantibodies by human-human hybridomas. J Clin Invest 70:205–208
Shulman M, Wilde CG, Köhler G (1978) A better line for making hybridomas secreting specific antibodies. Nature 267:296–298
Teng NNH, Lam KS, Riera FC, Kaplan HS (1983). Construction and testing of mousehuman heteromyelomas for human monoclonal antibody production. Proc Natl Acad Sci USA 80:7308–7312
Teng NNH, Kaplan HS, Herbert JM, Moore C, Douglas C, Wunderlich A, Braude AI (1985) Protection against gram-negative bacteremia and endotoxemia with human monoclonal IgM antibodies. Proc Natl Acad Sci USA 82:1790–1794
Thompson KM (1988) Human monoclonal antibodies. Immunol Today 9:113–117
References
Blalock JE, Johnson HM, Smith EM, Torres BA (1984) Enhancement of the in vitro antibody response by thyrotropin. Biochem Biophys Res Commun 125:30–34
Borrebaeck CAK (1983) In vitro immunization of mouse spleen cells and the production of monoclonal antibodies. Acta Chem Scand B37:647–648
Borrebaeck CAK, Möller SA (1986) In vitro immunization. Effect of growth and differentiation factors on antigen-specific B cell activation and production of monoclonal antibodies to autologous antigens and weak immunogens. J Immunol 136:3710–3715
Borrebaeck CAK (1986) In vitro immunizatin for production of murine and human monoclonal antibodies: present status. TIBTECH 6:147–153
Borrebaeck CAK, Danielsson L, Möller SA (1987) Human monoclonal antibodies produced from L-leucine methyl ester-treated and in vitro immunized peripheral blood lymphocytes. Biochem Biophys Res Commun 148:941–946
Borrebaeck CAK (1987) Development of in vitro immunization in murine and human hybridoma technique. J Pharm Biomed Anal 5:783–792
Borrebaeck CAK, Danielsson L, Möller SA (1988) Human monoclonal antibodies produced by primary in vitro immunization of peripheral blood lymphocytes. Proc Natl Acad Sci USA 85:3995–3999
Eddy EM, Müller CH, Lingwood CA (1985) Preparation of monoclonal antibody to sulfatoxygalactosylglycerolipid by in vitro immunization with glycolipid-glass conjugate. J Immunol Methods 81:137–146
Gratecos D, Astier M, Semeriva M (1987) A new approach to monoclonal antibody production: in vitro immunization with antigens on nitrocellulose using Drosophila myosin heavy chain as an example. J Immunol Methods 103:169–178
Hulette CM, Effros RB, Walford RL (1987) Immunization of normal human splenocytes in vitro to produce human monoclonal antibodies to cellular antigens. Tissue Antigens 30:25–33
Jokinen I, Poikonen K, Arvilommi H (1985) Synthesis of human immunoglobulins in vitro: comparison of two assays of secreted immunoglobulin. J Immunoassay 6:1–9
Kozbor D, Roder JC (1984) In vitro stimulated lymphocytes as a source of human hydridomas. Eur J Immunol 14:23–27
Lagace J, Brodeur BR (1985) Parameters affecting in vitro immunization of human lymphocytes. J Immunol Methods 85:127–136
Luzzati AL, Giacomini E, Frugoni P (1988) A two-stage culture system for induction of antibody-forming cell clones in cultures of normal human blood lymphocytes. J Immunol Methods 109:123–129
Masuho Y, Sugano T, Matsumoto Y, Sawada S, Tomibe K (1986) Generation of hybridomas producing human monoclonal antibodies against Herpes simplex virus after in vitro stimulation. Biochem Biophys Res Commun 135:495–500
Reading CL (1982) Theory and methods for immunization in culture and monoclonal antibody production. J Immunol Methods 53:261–291
Schelling M (1986) Increase of hybridoma formation by addition of dextran sulfate to in vitro immunization system. Hybridoma 5:159–161
Schlom J, Wunderlich D, Teramoto RA (1980) Generation of human monoclonal anti bodies reactive with human mammary carcinoma cells. Proc Natl Acad Sci USA 77:6841–6845
Sethi KK, Brandis H (1981) Generation of hybridoma cell lines producing monoclonal antibodies against Toxoplasma gondii or rabies following fusion of in vitro immunized spleen cells with myeloma cells. Ann Immunol 132C:29–39
Sikora K, Wright R (1981) Human monoclonal antibodies to lung cancer antigens. Br J Cancer 43:496–700
Strike LE, Devens BH, Lundak RL (1984) Production of human-human hybridomas secreting antibody to sheep erythrocytes after in vitro immunization. J Immunol 12:1798–1804
Terashima M, Shimada S, Komatsu H, Osawa T (1987) Production of human-human hybridomas secreting antibody to sheep erythrocytes after in vitro immunization of peripheral blood lymphocytes. Immunol Lett 15:89–93
Van Ness J, Laemmli UK, Pettijohn DE (1984) Immunization in vitro and production of monoclonal antibodies specific to insoluble and weak immunogenic proteins. Proc Natl Acad Sci USA 81:7897–7901
Wasserman RL, Budens RD, Thaxton ES (1986) In vitro stimulation prior to fusion generates antigen-binding human-human hybridomas. J Immunol Methods 93:275–283
References
Bendich A, Gabriel E, Machlin LJ (1986) Dietary vitamin E requirement for optimum immune responses in the rat. J Nutr 116:164–171
Colnago GL, Jensen LS, Long PL (1984) Effect of selenium on the development of immunity to coccidiosis in chickens. Poult Sci 63:1136–1143
Gabrysiak T (1989) Aktivierung humaner B-Lymphozyten durch Mitogene und Antigene in vitro. Bedeutung akzessorischer Immunzellen. Inauguraldiss, Göttingen
Gebremichael A, Levy EM, Corwin LM (1984) Adherent cell requirement for the efect of vitamin E on in vitro antibody synthesis. J Nutr 114:1297–1305
Gieseler RKH, Peters JH (1988) Accessory cells differentiated from bone marrow in a serumfree liquid culture system. Immunobiol 178:92–93
Gieseler RKH, Peters JH (1989) Myeloid bone marrow precursors of the rat develop into accessory dendritic cells at defined serum-free conditions. Exp Cell Biol 57:69
Lenzner S (1989) In vitro Stimulation der Antigen-spezifischen Immunglobulin-Synthese humaner B-Lymphozyten. Diplomarbeit, Göttingen
Najar HM, Boerner T, Ruppert J, Peters JH (1989) Immunoregulation by accessory cells and macrophages by noncyclic and cyclic nucleotides. Exp Cell Biol 57:110
Peters JH, Ruhl S, Friedrichs D (1987) Veiled accessory cells deduced from monocytes. Immunobiology 176:154–166
Pletsityi KD, Sukhikh GT, Davydova TV (1984) Vliianie vitamina E soderzhanie T- i B-limfotsitov v perifericheskoi krovi i nekotorye pokazateli nespetsificheskoi rezistentnosti. Vopr Pitan 4:42–44
Reddy PG, Morrill JL, Minocha HC, Morrill MB, Dayton AD, Frey RA (1986) Effect of supplemental vitamin E on the immune system of calves. J Dairy Sci 69:164–171
References
Borrebaeck CAK, Danielsson L, Möller SA (1988) Human monoclonal antibodies produced by primary in vitro immunization of peripheral blood lymphocytes. Proc Natl Acad Sci USA 85:3995–3999
Thiele DL, Kurosaka M, Lipsky PE (1983) Phenotype of the accesory cell necessary for mitogen-stimulated T and B cell responses in human peripheral blood: delineation by its sensitivity to the lysosomotropic agent, L-leucine methyl ester. J Immunol 131:2882–2290
References
Hoffmann MK, Chun M, Hirst JA, Mittler RS (1988) The IgM antibody response in cultures of mouse and human lymphoid cells. In: Borreback CAK (ed) In vitro immunization in hybridoma technology. Elsevier Amsterdam, pp 139–161
References
Agostino A, Idéo G (1965) Separation of large numbers of lymphocytes from human blood. Experientia 21:82–83
Borrebaeck CAK, Danielsson L, Möller SA (1988) Human monoclonal antibodies produced by primary in vitro immunization of peripheral blood lymphocytes. Proc Natl Acad Sci USA 85:3995–3999
Ocklind G (1988) All CD2-positive human lymphocytes rosette with sheep erythrocytes in the presence of polyethylene glycol. J Immunol Methods 112:169–172
References
Baron D, Hartlaub U (1987) Humane monoklonale Antikörper. Springer, Berlin Heidelberg New York, p 128
Borrebaeck CAK, Danielsson L, Möller SA (1988) Human monoclonal antibodies produced by primary in vitro immunization of peripheral blood lymphocytes. Proc Natl Acad Sci USA 85:3995–3999
Foon KA, Abrams PG, Rossio JL; Knost JA, Oldham RK (1983) Human hybridomas: comparison of human cell lines for production of human hybridomas and development of human hybridomas producing antigen-specific IgG using in vitro-immunized peripheral blood cells as fusing parameters. In: Boss BD, Langman R, Towbridge I, Dulbecco R (eds) Monoclonal antibodies and cancer. Academic Press, New York, pp 143–155
References
Hadden JW, Coffey RG (1982) Cyclic nucleotides in mitogen-induced lymphocyte proliferation. Immunol Today 3:299–304
References
Anderson MA, Gusella JF (1984) Use of Cyclosporin A in establising Epstein-Barr virus-transformed human lymphoblastoid cell lines. In Vitro 20:856–858
Knebel-Doeberitz M, von, Bornkamm GW, Hausen H zur (1983) Establishment of spontaneously outgrowing lymphoblastoid cell lines with Cyclosporin A. Med Microbiol Immunol 172:87–99
Miller G, Lipman M (1973) Release of infectious Epstein-Barr virus by transformed marmoset leukocytes. Proc Natl Acad Sci USA 70:190–194
References
Abken H, Jungfer H, Albert W, Willicke K (1986) Immortalization of human lymphocytes by fusion with cytoplasts of transformed mouse L cells. J Cell Biol 103:795–805
References
Abken H, Jungfer H, Albert W, Willicke K (1986) Immortalization of human lymphocytes by fusion with cytoplasts of transformed mouse L cells. J Cell Biol 103:795–805
Cepko C (1988) Immortalization of neural cells via oncogene transduction. Trends Neurol Sci 11:6–8
Land H, Parada LF, Weinberg RA (1983) Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature 304:596–602
Ruley HE (1983) Adenovirus early region 1A enables viral and cellular transforming genes to transform primary cells in culture. Nature 304:602–606
Stacey DW, Kung HF (1984) Tranformation of NIH 3T3 cells by microinjection of Ha-ras p21 protein. Nature 310:508–511
Willecke K, Abken HJ, Jungfer H, Barchet H (19878) Immortalisierung durch DNS-Übertragung. Offenlegungsschrift DE 3627326 Al, Deutsches Patentamt
References
Bischoff R, Eisert RM, Schedel I, Veinken J, Zimmermann U (1982) Human hybridoma cells produced by electrofusion. FEBS Lett 147:64–68
Köhler G, Milstein C (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256:495–497
Lo MMS, Tsong TY, Conrad MK, Strittmatter SM, Hester LD, Snyder SH (1984) Monoclonal antibody production by receptor-mediated electrically induced cell fusion. Nature 310:792–794
Ringertz NR, Savage RE (1976) Cell hybrids. Academic Press, New York
Vienken J, Zimmermann U (1985) An improved electrofusion technique for production of mouse hybridoma cells. FEBS Lett 182:278–279
Vienken J, Zimmermann U, Fouchard M, Zagury D (1983) Electrofusion of myeloma cells on the single cell level. FEBS Lett 163:54–56
Wojchowski DM, Sytkowski AJ (1986) Hybridoma production by simplified avidinmediated electrofusion. J Immunol Methol 90:173–177
References
Blas AL de, Ratnaparkhi MV, Mosimann JE (1983) Estimation of the number of monoclonal hybridomas in a cell-fusion experiment. In: Langone JJ, van Vunakis H (eds) Methods in enzymology, immunochemical techniques. Academic Press, New York, pp 36–39
References
Kontsekova E, Novak M, Kontsek P, Borecky L, Lesso J (1988) The effect of postfusion cell density on establishment of hybridomas. Folia Biol Praque 34:18–22
References
Marusich MF (1988) Efficient hybridoma production using previously frozen splenocytes. J Immunol Methods 124:155–159
Shi L, Xu H, Wang D, Dong Z (1987) An improving method to increase fusion rate by using in vivo myeloma cells from solid tumors in BALB/c mice. Chin J Microbiol Immunol 7:324–327
Shin S-I, van Diggelen OP (1977) In: McGarrity GJ, Murphy DG, Nichols WW (eds) Mycoplasma infection of cell cultures. New York, p 191
Wetzel GD, Kettman JR (1981) Activation of murine B lymphocytes, III. stimulation of B lymphocyte clonal growth with lipopolysaccharide and dextran sufate. J Immunol 126:723–728
References
Campbell AM (1985) Monoclonal antibody technology. Elsevier, Amsterdam
Civin CI, Banquerigo ML (1983) Rapid, efficient cloning of murine hybridoma cells in low gelaton temperature agarose. J Immunol Methods 61:1–8
References
Bell EB, Brown M, Ritternberg MB (1983) In vitro antibody synthesis in 20 μl hanging drops. J Immunol Methods 62:137–145
Campbell AM (1984) Cloning by limiing dilution. In: Campbell AM (ed) Monoclonal antibody technology. Elsevier, Amsterdam, pp 158–160
Coller HA, Coller BS (1983) Poisson statistical analysis of repetitive subcloning by the limiting dilution technique as a way of assessing hybridoma monoclonality. In: Langone JJ, Van Vunakis H (eds) Methods in Enzymol, vol 121. Academic Press. New York, pp 412–417
Harlow E, Lane D (1988) Single cell cloning. In: Harlow E, Lane D (eds) Antibodies. A laboratory manual. Cold Spring Harbor Laboratory, pp 219–230
Leitzke R, Unsicker K (1985) A statistical approach to determine monoclonality after limiting cell plating of a hybridoma clone. J Immunol Methods 76:223–228
McCullough KC, Butcher RN, Parkinson D (1983) Hybridoma cell lines secreting monoclonal antibodies against foot-and mouth disease virus (FMDV). II Cloning conditions. J Biol Stand 11:183
Thompson KM, Hough DW, Maddison PJ, Melamed MD, Hughes-Jones N (1986) The efficient production of stable, human monoclonal antibody-secreting hybridomas from EBV-transformed lymphocytes using the mouse myeloma X63-Ag8.653 as a fusion partner. J Immunol Methods 94:7–12
Further Reading
Bishop CE (1981) A miniaturised single-step method of cell cloning. J Immunol Methods 46:47–51
Hlinak A, Jahn S, Grunow R, Mehl M, Heider G, Baehr R von (1987) Optimierungsversuche zur Klonierung von Maus-Maus- und Mensch-Maus-Hybridomen unter Verwendung verschiedener Feederzelltypen. Mh Vet-Med 42:801–804
Koziol JA (1988) Evaluation of monoclonality of cell line from sequential dilution assays. Part II. J Immunol Methods 107:151–152
Koziol JA, Ferrari C, Chisari FVs (1987) Evaluation of monoclonality of cell lines from sequential dilution assays. J Immunol Methods 105:139
Makowski F, Joffe MI, Rittenberg MB (1986) Single cell cloning of Epstein-Barr virus transformed cells in 20 μl hanging drops. J Immunol Methods 90:85–87
Underwood PA, Bean PA (1988) Hazards of the limiting-dilution method of cloning hybridomas. J Immunol Methods 107:119–128
Further reading
Dangl JL, Herzenberg LA (1982) Selection of hybridomas and hybridoma variants using the fluorescence activated cell sorter. J Immunol Methods 52:1–14
Melamed MR, Lindmo T, Mendelsohn ML (1990) Flow cytometry and sorting. Wiley-Liss, New York
Ormerod MG (1990) Flow cytometry. Oxford University Press, Oxford
Parks DR, Herzenberg LA (1984) Fluorescence-activating cell sorting: theory, experimental optimization, and applications in lymphoid cell biology. Methods Enzymol 108:197–241
Shapiro HM (1988) Practical flow cytometry. Liss, New York
Van Dilla MA, Dean PN, Laerum OD, Melamed MR (1985) Flow cytometry: instrumentation and data analysis. Academic Press, London
Yen A (1989) Flow cytometry: advanced research and clinical applications. Vols I and II, CRC Press, Boca Raton
References
Lane RD, Crissman RS, Ginn S (1986) High efficiency fusion procedure for producing monoclonal antibodies against weak immunogens. Methods Enzymol 121:183–192
Neumann E, Schaefer-Ridder M, Wang Y, Hofschneider PH (1982) Gene transfer into mouse myeloma cells by electrofusion in high electric fields. EMBO J 1:841–845
References
Ossendorp FA, Bruning PF, Van den Brink JAM, De Boer M (1989) Efficient selection of high-affinity B cell hybridomas using antigen-coated magnetic beads. J Immunol Methods 120:191–200
Rüker F, Reiter S, Jungbauer A, Liegl W, Himmler G, Steinkellner H, Wenisch E, Steindl F, Wagner K, Katinger H (1987). Self-hybridization of hybridomas leads to stabilization of clones and increased yield of monoclonal antibodies. Dev Biol Stand 66:71–74
Siraganian RP, Fox PC, Berenstein EH (1983) Methods of enhancing the frequency of antigen-specific hybridomas. Methods Enzymol 92:17–26
Stähli C, Staehelin T, Miggiano V (1983) Spleen cell analysis and optimal immunization for high-frequency production of specific hybridomas. In: Langone JJ, van Vunakis H (Eds) Methods in enzymology, Immunochemical Techniques. Academic Press, New York, pp 26–36
Wang L, Feingers J, Gorsky Y, Catalano-Sherman J, Inbar M (1986) Monoclonal antibodies embedded in their hybridoma cells: an immunodiagnostic concept. Hybridoma 5:237–242
References
Aguila HL, Pollock RR, Spira G, Sharff MD (1986) The production of more useful monoclonal antibodies. 2. The use of somatic-cell genetic recombinant DNA technology to tailor-make monoclonal antibodies. Immuno Today 7:380–383
Alberini C, Biassoni R, DeAmbrtosis S, Vismara D, Sitia R (1987) Differentiation in the murine B cell lymphoma I.29: individual μ+ clones may be induced by lipopolysaccharide to both IgM secretion and isotype switching. Eur J Immunol 17:555–562
Brüggemann M, Free J, Diamond A, Howard J, Cobbold S, Waldmann H (1986) Immunolglobulin heavy chain locus of the rat: striking homology to mouse antibody genes. Proc Natl Acad Sci USA 83:6075–6079
Cavalli-Sforza LL, Lederberg J (1955) Isolation of pre-adaptive mutants in bacteria by sib selection. Genetics 41:367–381
Hale G, Cobbold SP, Waldman H, Easter G, Matejtschuk P, Coobs RRA (1987) Isolation of low-frequency class-switch variants from rat hybrid myelomas. J Immunol Methods 103:59–67
Kaminski MS, Kitamura K, Maloney DG, Campbelld MJ, Levy R (1986) Importance of antibody isotype in monoclonal anti-idiotype therapy of a murine B cell lymphoma. A study of hybridoma class switch variants. J Immunol 136:1123–1130
Kiesel S, Haas R, Moldenhauer G, Kvalheim G, Pezzutto A, Doerken B (1987) Removal of cells from a malignant B-cell line from bone marrow with immunomagnetic beads and with complement and immunoglobulin switch variant mediated cytolysis. Leuk Res 11:119–125
Kipps TJ (1985) Switching the isotype of monoclonal antibodies. In: Springer TA (ED) Hybridoma technology in the biosciences and medicine. Plenum, New York, pp 89–101
Komori S, Yamasaki N, Shigeta M, Isojima S, Watanabe T (1988) Production of heavy-chain class switch variants of human monoclonal antibodies by recombinant DNA technology. Clin Exp Immunol 71:508–516
Morrison SL (1985) Transfectomas provide novel chimeric antibodies. Science 229:1201–1207
Müller CE, Rajewsky K (1983) Isolation of immunoglobulin class switch variants from hybridoma lines secreting anti-idiotype antibodies by sequential sublining. J Immunol 131:877–881
Pluschke G, Bordmann G (1987) Isolation of rat immunoglobulin class switch variants of rat-mouse hybridomas by enzyme-linked immunosorbent assay and sequential sublining. Eur J Immunol 17:413–416
Preud’Homme JL, Birshtein BK, Sharff MD (1975) Variants of a mouse myeloma cell line that synthesize immunoglobulin heavy chains having an altered serotype. Proc Natl Acad Sci USA 72:1427–1430
Radbruch A (1986) Isotype switch variants. In: Weir DM (ed) Handbook of experimental immunology, 4th edn. Blackwell, Oxford, pp 110.1–110.12
Schmitz J, Radbruch A (1989) An interleukin 4-induced DNase I hypersensitive site indicates opening of the gamma 1 switch region prior to switch recombination. Int Immunol 1:570–575
Spira G, Bargellesi A, Pollock RR, Aguila HL, Scharff MD (1985) The generation of better monoclonal antibodies through somatic mutation. In: Springer TA (ed) Hybridoma technology in the biosciences and medicine. Plenum, New York, pp 77–88
References
Croce CM, Linnenback A, Hall W, Steplewski Z, Koprowski H (1980) Production of human hybridomas secreting antibodies to measles virus. Nature 288:488489
Koropatnik J, Pearson J, Harris JF (1988) Extensive loss of antibody production in heteromyeloma hybridoma cells. Mol Biol Med 5:69–83
Rushton AR (1976) Quantitative analysis of human chromosome segregation in man-mouse somatic cell hybrids. Cytogenet Cell Genet 17:343–254
References
Aguila HL, Pollock RR, Spira G, Scharff MD (1986) The production of more useful monoclonal antibodies. 2. The use of somatic-cell genetic recombinant DNA technology to tailor-make monoclonal antibodies. Immunol Today 7:380–383
Boulianne G, Hozumi N, Shulman MJ (1984) Production of functional chimaeric mouse/human antibody. Nature 312:643–646
Brennan M, Davison PF, Paulus H (1985) Preparation of bispecific antibodies by chemical recombination of monoclonal immunoglobulin G1 fragments. Science 229:81–83
Burnett KG, Martinis J, Bartholomew RM (1985) Production of bifunctional antibodies by hybridoma technology. In: Cheremisinoff PN, Quellette RP (Eds) Biotechnology: applications and research. Technomic, Lancaster PA (USA), pp 401–409
Campbell AM, Whitford P, Leake RE (1987) Human monoclonal antibody multispecificity. Br J Cancer 56:709–713
Corvalan JRF, Smith W (1987) Construction and characterization of a hybrid-hybrid monoclonal antibody recognizing both carcinoembryonic antigen (CEA) and vinca alkaloids. Cancer Immunol Immunother 24:127–132
De Lau WBM, Van Loon AE, Heije K, Valerio D, Bast BJEG (1989) Production of hybrid hybridomas based on HAT-neomycin double mutants. J Immunol Methods 117:1–8
Kang AS, Burton DR, Lerner RA (1991) Combinatorial immunoglobulin libraries in phage lambda. In: Lerner R, Burton DR (eds) Methods: a companion to methods in enzymology 2 (2), 111–118
Klausner A (1987) Second-generation antibodies: stage set for „immunological star wars”. Biotechnology 5:867–868
Komori S, Yamasaki N, Shigeta M, Isojima S, Watanabe T (1988) Production of heavy-chain class switch variants of human monoclonal antibodies by recombinant DNA technology. Clin Exp Immunol 71:508–516
Lanziavecchia A, Scheidegger D (1987) The use of hybrid hybridomas to target human cytotoxic T lymphocytes. Eur J Immunol 17:105–111
Martinis J, Kull JF, Franz G, Bartholomew RM (1982) Monoclonal antibodies with dual specificity. Protides Biol Fluids 30:311–316
Milstein C, Cuello AC (1983) Hybrid hybridomas and their use in immunohistochemistry. Nature 305:537–540
Milstein C, Cuello AC (1984) Hybrid hybridomas and the production of bi-specific monoclonal antibodies. Immunol Today 5:299–304
Morrison SL (1985) Transfectomas provide novel chimeric antibodies. Science 229:1202–1207
Morrison SL, Johnson M J, Herzenberg LA, Oi VT (1984) Chimeric human antibody molecules: mouse antigen-binding domains with human constant region domains. Proc Natl Acad Sci USA 81:6851–6855
Nisonoff A, Mandy WJ (1962) Quantitative estimation of the hybridization of rabbit antibodies. Nature 194:355–359
Nolan O, O’Kennedy R (1990) Bifunctional antibodies: concept, production and applications. Biochim Biophys Acta 1040:1–11
Reading CL (1983) European Patent Application No82303197.6, Publication No0068763
Runge MS, Bode C, Savard CE, Matsueda GR, Haber E (1990) Antibody-directed fibrinolysis: abispecific (Fab’)2 that binds to fibrin and tissue plasminogen activator. Bioconjug Chem 1:274–277
Staerz UD, Bevan MJ (1986) Hybrid hybridoma producing a bispecific monoclonal antibody that can focus effector T-cell activity. Proc Natl Acad Sci USA 83:1453–1457
Tutt A, Greenman J, Stevenson GT, Glennie MJ (1991) Bispecific F(ab’gamma) 3 antibody derivatives for redirecting unprimed cytotoxic T cells. Eur J Immunol 21:1351–1358
Winter G, Milstein C (1991) Man-made antibodies. Nature 349:293–299
References
Baumgarten H, Kürzinger K (1989) Designation of antibodies and their derivatives. Suggestions for a general nomeclature. J Immunol Methods 122:1–5
Bernard A, Boumsell L, Dausset J, Milstein C, Schlossman SF (1984) Leucocyte typing. Human leukocyte differentiation antigens detected by monoclonal antibodies. Springer, Berlin Heidelberg New York pp 133–134
Bulletin of the World Health Organization (1978) Proposed rules for the designation of immunoglobulins of animal origin. Bull WHO 56:815–817
Erber WN (1990) Human leukocyte differentiation antigens: review of the CD nomenclature. Pathology 22:61–69
Knapp W, Rieber P, Dörken B, Schmidt RE, Stein H, vd Borne K (1989a) Leucocyte typing IV. Oxford University Press, Oxford
Knapp W, Rieber P, Dörken B, Schmidt RE, Stein H, vd Borne K (1989b) Towards a better definition of human leucocyte surface molecules. Immunol Today 10:253–258
McMichael AJ (1987) Leucocyte typing III. Oxford University Press, Oxford
Reinherz EL, Haynes BF, Nadler LM, Bernstein ID (1986) Leukocyte typing II. Springer, Berlin Heidelberg New York
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Baron, D. et al. (1992). Production of Hybridomas. In: Peters, J.H., Baumgarten, H. (eds) Monoclonal Antibodies. Springer Laboratory. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-74532-4_6
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