van Erp R, Adorf M, van Sommeren A P, Schönherr O T, Gribnau T C
Clinical Lab Systems Research Unit, Organon Teknika B.V., Boxtel, The Netherlands.
J Biotechnol. 1991 Oct;20(3):235-48. doi: 10.1016/0168-1656(91)90285-4.
The long-term cultivation of hybridoma cells in hollow fibre bioreactors using serum-free medium, was monitored with respect to quantitative and qualitative aspects of the produced mAbs, cell viability, LDH and proteolytic activity. During the culture periods of hybridoma cells producing mAb OT-1C and 3A, the mAb concentration showed a decreasing trend with a concomitant increase of IgG fragments. The major IgG fragments did not bind the antigen and the molecular weights were significantly different from the corresponding IgG heavy and light chains. In addition, a good correlation was found between cell lysis, the presence of acid protease(s) and IgG fragments. The physicochemical and immunochemical properties of the "intact" mAbs (such as molecular weights, IEF patterns and affinity) did not change significantly during the culture period.
使用无血清培养基在中空纤维生物反应器中对杂交瘤细胞进行长期培养，针对所产生单克隆抗体的定量和定性方面、细胞活力、乳酸脱氢酶（LDH）及蛋白水解活性进行了监测。在产生单克隆抗体OT-1C和3A的杂交瘤细胞培养期间，单克隆抗体浓度呈下降趋势，同时IgG片段增加。主要的IgG片段不与抗原结合，且分子量与相应的IgG重链和轻链显著不同。此外，在细胞裂解、酸性蛋白酶的存在与IgG片段之间发现了良好的相关性。“完整”单克隆抗体的物理化学和免疫化学特性（如分子量、等电聚焦模式和亲和力）在培养期间没有显著变化。
