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利用高度稳定的 ssDNA 适体进行 CD30 表达淋巴瘤的免疫治疗。

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

机构信息

Department of Pathology and Genomic Medicine, Houston Methodist Hospital, 6565 Fannin St., Houston, TX 77030, USA.

出版信息

Biomaterials. 2013 Nov;34(35):8909-17. doi: 10.1016/j.biomaterials.2013.07.099. Epub 2013 Aug 19.

Abstract

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 led to apoptosis of ALCL cells. Immunotherapy using aptamer-based co-stimulation provides an alternative to antibodies, and has potential to transform cancer treatment.

摘要

CD30 在霍奇金淋巴瘤和间变性大细胞淋巴瘤中高度表达,使其成为治疗的一个有吸引力的靶点。我们描述了通过杂交 SELEX 方法生成结合 CD30 的血清稳定的 ssDNA 适体。所选适体与 CD30 具有高亲和力和特异性。进一步优化适体得到了一个短的、截短的变体,其亲和力比其较长的对应物高 50 倍。多价适体能够诱导 CD30 受体的寡聚化,并有效地激活下游信号转导,导致 ALCL 细胞凋亡。基于适体的免疫疗法提供了一种替代抗体的方法,有可能改变癌症治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cab/3784013/78e369a1b9aa/nihms511725f1a.jpg

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