Chida J
Gan To Kagaku Ryoho. 1984 Jan;11(1):157-64.
Generation of human monoclonal antibodies by human-human hybridomas was briefly reviewed. Monoclonal antibodies derived from human lymphocytes, once produced, would be better than those that are animal-derived with regard to in vivo use, such as immunotherapy by immunotoxin and diagnosis by antibody-targeted radioisotope imaging in the cancer patient. To date, very few human monoclonal antibodies, even against conventional antigens, have been reported. Their development by hybridoma techniques has been hampered for a variety of reasons of which the most important is probably the lack of reliable methods for antigen specific stimulation of human lymphocytes. A second problem would be the human myeloma lines for the fusion partner. Thus, we selected GM 1500 6TG-A1 2 line as the fusion partner and tested their ability to form hybrids with human spleen cells, secrete monoclonal immunoglobulin (Ig), clone, and maintain Ig secretion with the same Ig composition. The results were somewhat disappointing in regard to hybrid formation (5 X 10(-6), antibody secretion(0.1 approximately 100 micrograms/ml, majority approximately 1 microgram/ml), and stability in comparison with their murine counterparts. It is encouraging, however, that some cloned hybridomas produced large quantities (approximately 100 micrograms/ml) of IgM, which were nearly equivalent to those of murine hybridomas, for at least 6 month after fusion. The other available human myeloma lines have been reported to have similar or inferior characteristics to GM 1500 6TG line. The successful development of human-derived monoclonal antibodies would depend upon improvements in in vitro primary immunization of peripheral blood mononuclear cells as well as in establishing novel human myeloma or B cell lines, if possible Ig non secretors.
简要回顾了通过人-人杂交瘤产生人单克隆抗体的情况。源自人淋巴细胞的单克隆抗体一旦产生,在体内应用方面,如通过免疫毒素进行免疫治疗以及在癌症患者中通过抗体靶向放射性同位素成像进行诊断,将比动物源单克隆抗体更具优势。迄今为止,即使是针对传统抗原的人单克隆抗体也鲜有报道。由于多种原因,利用杂交瘤技术开发此类抗体受到了阻碍,其中最重要的原因可能是缺乏可靠的方法来对抗原进行特异性刺激以激活人淋巴细胞。第二个问题是用于融合的人骨髓瘤细胞系。因此,我们选择了GM 1500 6TG-A1 2细胞系作为融合伙伴,并测试了它们与人类脾细胞形成杂交瘤、分泌单克隆免疫球蛋白(Ig)、克隆以及维持相同Ig组成的Ig分泌能力。在杂交瘤形成(5×10⁻⁶)、抗体分泌(0.1至约100微克/毫升,大多数约为1微克/毫升)以及与鼠源杂交瘤相比的稳定性方面,结果有些令人失望。然而,令人鼓舞的是,一些克隆的杂交瘤在融合后至少6个月内产生了大量(约100微克/毫升)的IgM,其产量几乎与鼠源杂交瘤相当。据报道,其他可用的人骨髓瘤细胞系具有与GM 1500 6TG细胞系相似或更差的特性。人源单克隆抗体的成功开发将取决于外周血单个核细胞体外初次免疫方法的改进,以及建立新型的人骨髓瘤或B细胞系(如果可能的话,Ig非分泌细胞系)。