Bosslet K, Steinstraesser A, Hermentin P, Kuhlmann L, Bruynck A, Magerstaedt M, Seemann G, Schwarz A, Sedlacek H H
Research Laboratories of Behringwerke AG, Marburg/Lahn, Germany.
Br J Cancer. 1991 May;63(5):681-6. doi: 10.1038/bjc.1991.155.
A two phase radioimmunotherapy based on bispecific MAbs in which one arm recognises a tumour antigen and the other a radiolabelled chelate, may prove more effective in the treatment of carcinomas than currently available immunotherapies. To establish this system we first showed that penetration into human carcinoma xenografts as well as long term retention of intact MAb outside the carcinoma cells can be obtained. Epitope saturation was not obtained however, despite the large MAb doses injected i.v. for 10 days. We then generated hybridomas producing high avidity anti-metal chelate MAbs (anti-DTPA-Y). These hybridomas were fused with hybridomas producing MAbs against CEA or GIT-mucin, and stable bispecific MAb producing quadromas were obtained. For the anti-GIT-mucin x anti-chelate MAb a purification procedure based on double anti-idiotype affinity chromatography was shown to result in greater than 95% pure bispecific immunoreactive MAb. Comparative in vivo stability studies profiled DTPA-Y as the chelate of choice for in vivo application.
一种基于双特异性单克隆抗体的两阶段放射免疫疗法，其中一条臂识别肿瘤抗原，另一条臂识别放射性标记的螯合物，在治疗癌症方面可能比目前可用的免疫疗法更有效。为了建立这个系统，我们首先表明，可以实现对人癌异种移植物的渗透以及完整单克隆抗体在癌细胞外的长期保留。然而，尽管静脉注射大剂量单克隆抗体持续10天，仍未获得表位饱和。然后，我们制备了产生高亲和力抗金属螯合单克隆抗体（抗DTPA-Y）的杂交瘤。这些杂交瘤与产生抗CEA或胃肠道粘蛋白单克隆抗体的杂交瘤融合，获得了产生稳定双特异性单克隆抗体的四瘤细胞系。对于抗胃肠道粘蛋白x抗螯合单克隆抗体，基于双抗独特型亲和色谱的纯化程序显示可产生纯度大于95%的双特异性免疫反应性单克隆抗体。体内稳定性比较研究表明，DTPA-Y是体内应用的首选螯合物。
