Ehrlich P H, Moustafa Z A, Justice J C, Harfeldt K E, Ostberg L
Monoclonal Antibody Department, Sandoz Pharmaceuticals Corporation, East Hanover, NJ 07936.
Hybridoma. 1988 Aug;7(4):385-95. doi: 10.1089/hyb.1988.7.385.
We have shown previously that human monoclonal antibodies are not very immunogenic in rhesus monkeys, with only one monkey out of five mounting an anti-monoclonal antibody response. Two additional monkeys have been injected multiple times with much larger amounts of one human monoclonal antibody. No anti-antibody response has been detected in these monkeys. Structural changes that occur in the monoclonal antibodies over time in vivo have been investigated by Western Blots using anti-idiotypic antisera. Sodium dodecyl sulfate gel electrophoresis reveals that very little antibody has altered molecular weight. Isoelectric focusing patterns change more dramatically. Forms of the antibodies with lower isoelectric points appear in the serum. These forms have a similar in vivo half-life as the freshly prepared antibody. Very low pI forms of the monoclonal antibodies are not detected in the serum. Isoelectric focusing can be used to determine the in vivo or in vitro condition of a monoclonal antibody preparation. Finally, the monkey anti-human IgG that arose in the single monkey studied previously has been further characterized.
我们之前已经表明，人源单克隆抗体在恒河猴中免疫原性不强，五只猴子中只有一只产生了抗单克隆抗体反应。另外两只猴子多次注射了大量的一种人源单克隆抗体。在这些猴子中未检测到抗抗体反应。使用抗独特型抗血清通过蛋白质印迹法研究了单克隆抗体在体内随时间发生的结构变化。十二烷基硫酸钠凝胶电泳显示，很少有抗体发生分子量改变。等电聚焦图谱变化更为显著。血清中出现了等电点较低的抗体形式。这些形式的抗体在体内的半衰期与新制备的抗体相似。血清中未检测到极低等电点形式的单克隆抗体。等电聚焦可用于确定单克隆抗体制剂的体内或体外状态。最后，对之前研究的那只猴子中产生的猴抗人IgG进行了进一步表征。
