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
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
收藏
页码:386 / 397
页数:12
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