Immunotherapy of CD30-expressing lymphoma using a highly stable ssDNA aptamer.

Immunotherapy of CD30-expressing lymphoma using a highly stable ssDNA aptamer.
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DOI:
10.1016/j.biomaterials.2013.07.099
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发表时间:
2013-11
期刊:
影响因子:
14
通讯作者:
Zu, Youli
Zu, Youli
中科院分区:
工程技术1区
文献类型:
--
作者:
Parekh, Parag;Kamble, Sanchit;Zhao, Nianxi;Portier, Bryce P.;Zu, Youli

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CD30在霍奇金淋巴瘤和间变性大细胞淋巴瘤中高度表达,使其成为有吸引力的治疗靶点。我们描述了通过混合SELEX方法结合CD30的血清稳定的单链DNA适配子的产生。所选适配子与CD30结合具有较高的亲和力和特异性。对适配子的进一步优化导致了一个短的、截断的突变体,其亲和力比长的突变体高50倍。该多价适配子能够诱导CD30受体的寡聚化,并有效地激活下游信号,从而导致ALCL细胞凋亡。使用基于适体的共刺激的免疫疗法提供了抗体的替代方案,并有可能改变癌症治疗。
CD30 is highly expressed on Hodgkins lymphoma and anaplastic large cell lymphoma, making it an attractive target for therapy. We describe the generation of serum-stabilized ssDNA aptamers that bind CD30 via a hybrid SELEX methodology. The selected aptamer bound CD30 with high affinity and specificity. Further optimization of the aptamer led to a short, truncated variant with a 50-fold higher affinity than its longer counterpart. The multivalent aptamer was able to induce oligomerization of CD30 receptors and, in effect, activate downstream signaling, which lead to apoptosis of ALCL cells. Immunotherapy using aptamer-based co-stimulation provides an alternative to antibodies, and has potential to transform cancer treatment.
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