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适体-抗体复合物(寡体)作为一种新型的靶向癌症治疗药物的递药平台。

An aptamer-antibody complex (oligobody) as a novel delivery platform for targeted cancer therapies.

机构信息

Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 410-769, Republic of Korea.

Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 410-769, Republic of Korea; Graduate School of Cancer Science and Policy, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 410-769, Republic of Korea.

出版信息

J Control Release. 2016 May 10;229:1-9. doi: 10.1016/j.jconrel.2016.03.006. Epub 2016 Mar 5.

Abstract

Aptamers have recently emerged as reliable and promising targeting agents in the field of biology. However, their therapeutic potential has yet to be completely assessed due to their poor pharmacokinetics for systemic administration. Here, we describe a novel aptamer-antibody complex, designated an "oligobody" (oligomer+antibody) that may overcome the therapeutic limitations of aptamers. To provide proof-of-principle study, we investigated the druggability of oligobody in vivo using cotinine conjugated t44-OMe aptamer, which is specific for the sequence of pegaptanib, and an anti-cotinine antibody. The antibody part of oligobody resulted in extended in vivo pharmacokinetics of the aptamer without influencing its binding affinity. Moreover, the aptamer of oligobody penetrated deeply into the tumor tissues whereas the anti-VEGF antibody did not. Finally, the systemic administration of this oligobody reduced the tumor burden in a xenograft mouse model. Together, these results suggested that our oligobody strategy may represent a novel platform for rapid, low-cost and high-throughput cancer therapy.

摘要

适体作为一种可靠且有前景的生物领域靶向试剂最近崭露头角。然而,由于其全身给药时的药代动力学特性较差,其治疗潜力尚未得到全面评估。在这里,我们描述了一种新型的适体-抗体复合物,称为“寡聚物”(寡聚物+抗体),它可能克服适体的治疗限制。为了提供原理验证研究,我们使用针对 pegaptanib 序列的结合物 cotinine 共轭 t44-OMe 适体和抗 cotinine 抗体研究了寡聚物在体内的成药性。寡聚物的抗体部分延长了适体的体内药代动力学特性,而不影响其结合亲和力。此外,寡聚物的适体能够深入穿透肿瘤组织,而抗 VEGF 抗体则不能。最后,该寡聚物的全身给药可减少异种移植小鼠模型中的肿瘤负担。总之,这些结果表明,我们的寡聚物策略可能代表了一种用于快速、低成本和高通量癌症治疗的新平台。

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