多特异性单克隆抗体MsMab-2可识别异柠檬酸脱氢酶1（IDH1）的R132L突变以及异柠檬酸脱氢酶2（IDH2）的R172M突变。
Multi-specific monoclonal antibody MsMab-2 recognizes IDH1-R132L and IDH2-R172M mutations.
作者信息
Ogasawara Satoshi, Kaneko Mika Kato, Tsujimoto Yuta, Liu Xing, Kato Yukinari
机构信息
Department of Regional Innovation, Tohoku University Graduate School of Medicine , Aoba-ku, Sendai, Miyagi, Japan .
出版信息
Monoclon Antib Immunodiagn Immunother. 2013 Dec;32(6):377-81. doi: 10.1089/mab.2013.0050.
Mutations of isocitrate dehydrogenase 1/2 (IDH1/2) produce oncometabolite R(-)-2-hydroxyglutarate in several tumors. Arginine 132 (R132) of IDH1 and arginine 172 (R172) of IDH2 are functionally important residues. Although MsMab-1 monoclonal antibody (MAb), which is multi-specific for mutated IDH1/2, has been established, MsMab-1 does not react with all IDH1/2 mutations. Herein, we immunized rats with IDH1-R132L peptide, and screened IDH1-R132L-reactive/IDH1-wild-type non-reactive MAbs in enzyme-linked immunosorbent assay. Unexpectedly, the newly established MsMab-2 MAb recognized not only IDH1-R132L but also IDH2-R172M in Western blot analyses, neither of which was detected by MsMab-1. Taken together, the combination of MsMab-1 and MsMab-2 could be useful in diagnosis of mutated IDH1/2-bearing tumors.
异柠檬酸脱氢酶1/2（IDH1/2）突变在多种肿瘤中产生致癌代谢物R(-)-2-羟基戊二酸。IDH1的精氨酸132（R132）和IDH2的精氨酸172（R172）是功能上重要的残基。尽管已建立了对突变型IDH1/2具有多特异性的MsMab-1单克隆抗体（MAb），但MsMab-1并非能与所有IDH1/2突变发生反应。在此，我们用IDH1-R132L肽免疫大鼠，并在酶联免疫吸附测定中筛选出与IDH1-R132L反应/与IDH1野生型不反应的单克隆抗体。出乎意料的是，新建立的MsMab-2单克隆抗体在蛋白质印迹分析中不仅识别IDH1-R132L，还识别IDH2-R172M，而MsMab-1均未检测到这两种突变。综上所述，MsMab-1和MsMab-2的组合可能有助于诊断携带IDH1/2突变的肿瘤。
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