Ehrlich P H, Harfeldt K E, Justice J C, Moustafa Z A, Ostberg L
Hybridoma. 1987 Apr;6(2):151-60. doi: 10.1089/hyb.1987.6.151.
Five rhesus monkeys were injected multiple times over several months with two different human IgG1 monoclonal antibodies, both directed against human cytomegalovirus. Three monkeys each injected four times with monoclonal antibody EV2-7 for over 200 days showed no response other than a normal decay in antibody level. The in vivo half life of this antibody was substantially longer when measured with an idiotype-specific two site immunoassay than with radiolabeled antibody, indicating that the iodination procedure greatly affected the stability of the antibody. Although there was considerable individual variation in the half-life of EV2-7, from 8.9 to 30.5 days, the half-life was fairly long, especially considering the size of the monkeys. Two monkeys were injected with monoclonal antibody EV1-15. One monkey has responded in a similar manner to the EV2-7-injected monkeys. However, the other monkey has produced an anti-idiotypic antibody (or antibodies) of high affinity. It is possible that this response was triggered by the unusual physical nature of antibody EV1-15 or the effect of the species difference between human and rhesus monkey. In any case, the results from these five monkeys indicate that human monoclonal antibodies should have a significant advantage over mouse monoclonal antibodies for in vivo therapeutic applications.
在几个月的时间里，给五只恒河猴多次注射了两种不同的人IgG1单克隆抗体，这两种抗体均针对人巨细胞病毒。三只猴子各自接受了超过200天、共四次的单克隆抗体EV2-7注射，除了抗体水平正常下降外，未出现其他反应。用独特型特异性双位点免疫测定法测量时，该抗体的体内半衰期比用放射性标记抗体测量时长得多，这表明碘化过程极大地影响了抗体的稳定性。尽管EV2-7的半衰期存在相当大的个体差异，从8.9天到30.5天不等，但半衰期相当长，尤其是考虑到猴子的体型。给两只猴子注射了单克隆抗体EV1-15。一只猴子的反应与注射EV2-7的猴子类似。然而，另一只猴子产生了高亲和力的抗独特型抗体。这种反应可能是由抗体EV1-15不寻常的物理性质或人与恒河猴之间的物种差异效应引发的。无论如何，这五只猴子的结果表明，在体内治疗应用方面，人单克隆抗体应比小鼠单克隆抗体具有显著优势。
