Inhibition of cell proliferation by an anti-EGFR aptamer.
Inhibition of cell proliferation by an anti-EGFR aptamer.
复制标题
DOI：
10.1371/journal.pone.0020299
复制
发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Ellington AD
中科院分区：
文献类型：
--
作者：
Li N;Nguyen HH;Byrom M;Ellington AD
适体作为潜在的治疗药物继续受到人们的关注，用于治疗包括癌症在内的疾病。为了确定适配子是否最终被证明与其他临床生物聚合物(如抗体)一样有用，我们选择了针对重要临床靶点-人表皮生长因子受体(HEGFR)的适配子。最初的选择只产生了一个能与hEGFR结合的克隆，但进一步的突变和优化产生了一系列紧密结合的适体。选定的适体之一，E07，与野生型受体(Kd = 2.4nM)紧密结合。这种适配子可以与EGF竞争结合，结合EGFR上的一个新表位，还可以结合缺失突变体EGFRvIII，这种突变体在乳腺癌和肺癌中很常见，特别是在IV级多形性胶质母细胞瘤中，这种癌症已被证明对目前的治疗大多无效。该适配子与表达EGFR的细胞结合，阻断受体自磷酸化，并阻止三维基质中的肿瘤细胞增殖。简而言之，适体是一种很有希望作为抗肿瘤治疗药物进一步开发的候选药物。此外，适体E07很容易内化到表达EGFR的细胞中，这增加了它可能被用来护送其他抗肿瘤或造影剂的可能性。
Aptamers continue to receive interest as potential therapeutic agents for the treatment of diseases, including cancer. In order to determine whether aptamers might eventually prove to be as useful as other clinical biopolymers, such as antibodies, we selected aptamers against an important clinical target, human epidermal growth factor receptor (hEGFR). The initial selection yielded only a single clone that could bind to hEGFR, but further mutation and optimization yielded a family of tight-binding aptamers. One of the selected aptamers, E07, bound tightly to the wild-type receptor (Kd = 2.4 nM). This aptamer can compete with EGF for binding, binds to a novel epitope on EGFR, and also binds a deletion mutant, EGFRvIII, that is commonly found in breast and lung cancers, and especially in grade IV glioblastoma multiforme, a cancer which has for the most part proved unresponsive to current therapies. The aptamer binds to cells expressing EGFR, blocks receptor autophosphorylation, and prevents proliferation of tumor cells in three-dimensional matrices. In short, the aptamer is a promising candidate for further development as an anti-tumor therapeutic. In addition, Aptamer E07 is readily internalized into EGFR-expressing cells, raising the possibility that it might be used to escort other anti-tumor or contrast agents.
登录
查看更多内容
影响因子：
46.9
作者：
Dassie, Justin P.;Liu, Xiu-ying;Thomas, Gregory S.;Whitaker, Ryan M.;Thiel, Kristina W.;Stockdale, Katie R.;Meyerholz, David K.;McCaffrey, Anton P.;McNamara, James O., II;Giangrande, Paloma H.
通讯作者：
Giangrande, Paloma H.
影响因子：
4.8
作者：
Gan, Hui K.;Walker, Francesca;Johns, Terrance G.
通讯作者：
Johns, Terrance G.
影响因子：
--
作者：
Flynn JF;Wong C;Wu JM
通讯作者：
Wu JM
影响因子：
46.9
作者：
Judge, AD;Sood, V;MacLachlan, I
通讯作者：
MacLachlan, I
影响因子：
3.7
作者：
Jaramillo, Maria L.;Leon, Zully;McCourt, Maureen O'Connor
通讯作者：
McCourt, Maureen O'Connor