Marchitto K S, Kindsvogel W R, Beaumier P L, Fine S K, Gilbert T, Levin S D, Woodhouse C S, Morgan A C
NeoRx Corporation, Seattle, Washington 98119.
Prog Clin Biol Res. 1989;288:101-5.
The data presented demonstrate that a human-murine chimeric antibody has been generated that retains the immunoreactivity and has similar pharmacokinetic properties of its parent murine monoclonal antibody NRML-05. A competitive ELISA assay demonstrated that antigen reactivity of both parent and chimera were nearly identical. In a direct cell binding assay, NRML-05 and chimeric antibodies were immunoreactive, 81% and 83%, respectively. Scatchard Analysis of the antibodies indicate very similar affinities for NRML-05 (4.4 x 10(9) M-1) and chimera (2.7 x 10(9) M-1). Localization of the two antibodies to tumor xenografts in nude mice were very similar in biodistribution studies. The chimeric antibody is not as well recognized by antiglobulin from patients who have responded to non-idiotypic murine antibody determinants. Although this data does not predict how immunogenic a chimera would be in the clinical setting, it does suggest that patients without significant anti-idiotypic antiglobulin response could benefit from second and subsequent administrations with chimeric antibody. Even though anti-idiotypic responses may occur with the chimera, these may be reduced as a result of the presentation of these epitopes on the less immunogenic human constant domains.
所呈现的数据表明，已产生一种人鼠嵌合抗体，它保留了免疫反应性，并且具有与其亲本鼠单克隆抗体NRML-05相似的药代动力学特性。竞争性ELISA分析表明，亲本抗体和嵌合抗体的抗原反应性几乎相同。在直接细胞结合试验中，NRML-05和嵌合抗体具有免疫反应性，分别为81%和83%。对抗体的Scatchard分析表明，它们对NRML-05（4.4×10⁹ M⁻¹）和嵌合抗体（2.7×10⁹ M⁻¹）的亲和力非常相似。在生物分布研究中，两种抗体在裸鼠肿瘤异种移植物中的定位非常相似。对于已对非独特型鼠抗体决定簇产生反应的患者的抗球蛋白，嵌合抗体的识别效果不佳。尽管这些数据无法预测嵌合抗体在临床环境中的免疫原性如何，但确实表明，没有显著抗独特型抗球蛋白反应的患者可能会从第二次及后续使用嵌合抗体中受益。即使嵌合抗体可能会出现抗独特型反应，但由于这些表位在免疫原性较低的人恒定区上呈现，这些反应可能会减少。
