Multi-Specific Monoclonal Antibody MsMab-2 Recognizes IDH1-R132L and IDH2-R172M Mutations
Multi-Specific Monoclonal Antibody MsMab-2 Recognizes IDH1-R132L and IDH2-R172M Mutations
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DOI：
10.1089/mab.2013.0050
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发表时间：
2013-12-01
影响因子：
--
通讯作者：
Kato, Yukinari
中科院分区：
文献类型：
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作者：
Ogasawara, Satoshi;Kaneko, Mika Kato;Kato, Yukinari
异柠檬酸脱氢酶1/2（IDH 1/2）的突变在几种肿瘤中产生癌代谢物R（-）-2-羟基戊二酸。IDH 1的精氨酸132（R132）和IDH 2的精氨酸172（R172）是功能上重要的残基。尽管已经建立了对突变的IDH 1/2具有多特异性的MsMab-1单克隆抗体（MAb），但MsMab-1并不与所有IDH 1/2突变反应。本文以IDH 1-R132 L肽段免疫大鼠，通过酶联免疫吸附试验筛选IDH 1-R132 L反应性单克隆抗体和IDH 1-野生型非反应性单克隆抗体。出乎意料的是，新建立的MsMab-2单克隆抗体在Western印迹分析中不仅识别IDH 1-R132 L，而且识别IDH 2-R172 M，而MsMab-1不能检测到这两种抗体。总之，MsMab-1和MsMab-2的组合可用于诊断携带突变IDH 1/2的肿瘤。
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.