Preparation and properties of nido-carborane-specific monoclonal antibodies for potential use in boron neutron capture therapy for cancer.
Preparation and properties of nido-carborane-specific monoclonal antibodies for potential use in boron neutron capture therapy for cancer.
复制标题
尼多碳硼烷特异性单克隆抗体的制备和特性，可用于癌症的硼中子捕获疗法。
DOI：
10.1073/pnas.92.15.6986
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发表时间：
1995
影响因子：
11.1
通讯作者：
Hawthorne,MF
中科院分区：
文献类型：
--
作者：
Pak,RH;Primus,FJ;Rickard-Dickson,KJ;Ng,LL;Kane,RR;Hawthorne,MF
作为旨在开发用于将富硼分子递送至肿瘤细胞以用于硼中子捕获疗法的双特异性单克隆抗体系统的研究计划的第一步，产生针对阴离子巢式碳硼烷衍生物4-[7，8-二卡巴十二氢十一硼酸（-1）-7-基]丁酸的单克隆抗体（mAb）。鉴定了两种IgG亚类mAb，命名为HAW 101和HAW 102，其特异性结合阴离子巢式-碳硼烷半抗原，以及多种其他阴离子巢式-碳硼烷笼衍生物。利用表面等离子体共振技术测得HAW 101和HAW 102的亲和常数分别为1.9 × 10（9）和6.8 × 10（8）M-1。一系列不同的7-取代和7，8-二取代的阴离子巢式碳硼烷衍生物在竞争ELISA中与mAb HAW 101反应，而阴离子封闭多面体硼烷显示出可忽略不计的结合，表明开放巢式碳硼烷笼结构的作用。这些结果表明，结合阴离子巢式碳硼烷的mAb如HAW 101可用于开发用于特异性靶向和增强硼递送至肿瘤部位的双特异性mAb。
As the first step of a research program aimed at developing a bispecific monoclonal antibody system for the delivery of boron-rich molecules to tumor cells for boron neutron capture therapy, monoclonal antibodies (mAbs) were produced against an anionic nido-carborane derivative, 4-[7,8-dicarbadodecahydroundecaborat(-1)-7-yl]butanoic acid. Two IgG subclass mAbs, designated HAW101 and HAW102, were identified that specifically bound the anionic nido-carborane hapten, as well as a variety of other anionic nido-carborane cage derivatives. By using surface plasmon resonance technology, the affinity constants of HAW101 and HAW102 were determined to be 1.9 x 10(9) and 6.8 x 10(8) M-1, respectively. A diverse array of 7-substituted and 7,8-disubstituted anionic nido-carborane derivatives reacted with the mAb HAW101 in competition ELISA, whereas anionic closo-polyhedral boranes showed negligible binding, suggesting a role for the open nido-carborane cage structure. These results suggest that mAbs such as HAW101, which bind anionic nido-carboranes, are useful in the development of bispecific mAbs for specific targeting and enhanced boron delivery to tumor sites.