ESTABLISHMENT OF STABLE MOUSE HUMAN-HUMAN HYBRID CELL-LINES PRODUCING LARGE AMOUNTS OF ANTITETANUS HUMAN MONOCLONAL-ANTIBODIES WITH HIGH NEUTRALIZING ACTIVITY

被引：26

作者：

KAMEI, M ^{[1
]}

HASHIZUME, S ^{[1
]}

SUGIMOTO, N ^{[1
]}

OZUTSUMI, K ^{[1
]}

MATSUDA, M ^{[1
]}

机构：

[1] MORINAGA INST BIOL SCI,2-1-1 SHIMOSUEYOSHI,TSURUMI KU,YOKOHAMA,KANAGAWA 230,JAPAN

来源：

EUROPEAN JOURNAL OF EPIDEMIOLOGY | 1990年 / 6卷 / 04期

关键词：

HYBRID CELL LINES; ANTITETANUS MONOCLONAL ANTIBODIES; HUMAN MONOCLONAL ANTIBODIES; NEUTRALIZING ANTIBODIES;

D O I：

10.1007/BF00151713

中图分类号：

R1 [预防医学、卫生学];

学科分类号：

1004 ; 120402 ;

摘要：

To establish stable hybrid cell lines producing human anti-tetanus antibody with high toxin-neutralizing activity, peripheral lymphocytes from humans hyperimmunized with tetanus toxoid were, after in vitro antigen stimulation, fused with a mouse/human heteromyeloma or human lymphoblastoid cell line and cloned. Unlike the IgM secretors (six clones), the IgG secretors we obtained (six clones) produced anti-tetanus human monoclonal antibodies with high neutralizing activity (the highest one, cell line G2, 4.3 IU/100 mu-g IgG). Appropriate combinations of three or four kinds of monoclonal antibodies of the IgG type resulted in markedly increased neutralizing activity comparable with that of anti-tetanus human polyclonal immunoglobulin preparations currently used clinically on the basis of toxin-specific IgG content. Five of these cell lines produced 10 approximately 20 mu-g of antibody per ml for more than 3 months. The cell line G2 produced 6 mg of antibody per day in serum-free medium in a 500-ml bioreactor in perfusion culture and 13-104 mg in a nude mouse. These cell lines satisfied, for the first time, the minimal requirements for applying human monoclonal antibodies to clinical use.

引用

页码：386 / 397

页数：12

共 33 条

[1] Aleshkin V.A., Borisova V.N., Ponomaryova A.M., Popkov M.Y.U., Production of homologous tetanus antitoxin from commercial γ-globulin preparations, Proceedings of the 8th International Conference on Tetanus, pp. 285-290, (1989)
[2] Boyd J.E., Hastings I., Farzad Z., James K., McClelland D.B.L., Experiences in the production of human monoclonal antibodies to tetanus toxoid, Develop. Biol. Standard., 57, pp. 93-98, (1984)
[3] Ebisawa I., Matsuhashi C., Yamamoto A., Kurosu Y., Otsuka T., Clinical experiences in the use of intravenously injectable tetanus-immune human gamma globulin in TIG(i), Kansenshogaku Zasshi (J Jpn Assoc Infect Dis), 55, pp. 92-98, (1981)
[4] Gigliotti F., Insel R.A., Protective human hybridoma antibody to tetanus toxin, J. Clin. Invest., 70, pp. 1306-1309, (1982)
[5] Gigliotti F., Smith L., Insel R.A., Reproducible production of protective human monoclonal antibodes by fusion of peripheral blood lymphocytes with a mouse myeloma cell line, J. Infect. Dis., 149, pp. 43-47, (1984)
[6] Hashizume S., Mochizuki K., Murakami H., Yano T., Yasumoto K., Nomoto K., Serodiagnosis of cancer, using porcine antigens recognized by human monoclonal antibody, HB4C5, Biotherapy, 1, pp. 109-115, (1989)
[7] Hirata Y., Sugawara I., Characterization of mouse-human hybridoma as a useful fusion partner for the establishment of mouse-human-human hybridoma secreting anti-tetanus toxoid human monoclonal antibody of IgM or IgG class, Microbiol. Immunol., 31, pp. 231-245, (1987)
[8] Ichimori Y., Sasano K., Itoh H., Hitotsumachi S., Kimura Y., Kaneko K., Kida M., Tsukamoto K., Establishment of hybridomas secreting human monoclonal antibodies against tetanus toxin and hepatitis B virus surface antigen, Biochem. Biophys. Res. Commun., 129, pp. 26-33, (1985)
[9] Kozbor D., Roder J.C., Requirements for the establishment of high-titered human monoclonal antibodies against tetanus toxoid using the Epstein Barr virus technique, J. Immunol., 127, pp. 1275-1280, (1981)
[10] Kozbor D., Roder J.C., The production of monoclonal antibodies from human lymphocytes, Immunol. Today, 4, pp. 72-79, (1983)

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