Rational development of molecularly imprinted nanoparticles for blocking PD-1/PD-L1 axis.
Rational development of molecularly imprinted nanoparticles for blocking PD-1/PD-L1 axis.
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DOI：
10.1039/d2sc03412c
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发表时间：
2022-09-21
期刊：
影响因子：
8.4
通讯作者：
中科院分区：
文献类型：
--
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阻断PD-1/PD-L1免疫检查点已成为癌症免疫治疗中一种有前途的策略，其中单克隆抗体主要用作抑制剂。尽管它们取得了显著的成功，但基于单克隆抗体的治疗剂由于使用抗体而具有缺点，例如高成本、低稳定性和高频率的免疫相关不良反应。因此，可以解决这些问题的新型抗PD-1/PD-L1治疗剂具有重要意义。在此，我们报告了一种基于分子印迹聚合物（MIP）的PD-1纳米抑制剂，用于阻断PD-1/PD-L1轴。以PD-1的N-末端表位为结合位点，通过表位印迹技术，合理设计并改造了抗PD-1的纳米MIP。抗PD-1 nanoMIP显示出对PD-1的良好特异性和高亲和力，产生10−8 M水平的解离常数，远优于PD-1和PD-L1之间的解离常数。通过空间位阻，该抑制剂可以有效地阻断PD-1/PD-L1相互作用。此外，它可以有效地重新激活T细胞，逆转肿瘤细胞的化疗耐药性。因此，本研究不仅提供了一种新的和有前途的免疫检查点阻断抑制剂，而且还促进了MIP用于癌症免疫治疗的进一步发展。合理开发了阻断PD-1/PD-L1轴的纳米级分子印迹聚合物（MIP）。抗PD-1 nanoMIP能够有效阻断PD-1/PD-L1相互作用，重新激活T细胞，逆转肿瘤细胞的化疗耐药性。
Blocking the PD-1/PD-L1 immune checkpoint has emerged as a promising strategy in cancer immunotherapy, in which monoclonal antibodies are predominately used as inhibitors. Despite their remarkable success, monoclonal antibody-based therapeutics suffer from drawbacks due to the use of antibodies, such as high cost, low stability and high frequency of immune-related adverse effects. Therefore, novel anti-PD-1/PD-L1 therapeutics that can address these issues are of significant importance. Herein, we report a molecularly imprinted polymer (MIP) based PD-1 nano inhibitor for blocking the PD-1/PD-L1 axis. The anti-PD-1 nanoMIP was rationally designed and engineered by epitope imprinting using the N-terminal epitope of PD-1 as the binding site. The anti-PD-1 nanoMIP showed good specificity and high affinity towards PD-1, yielding a disassociation constant at the 10−8 M level, much better than that between PD-1 and PD-L1. Via steric hindrance, this inhibitor could effectively block PD-1/PD-L1 interaction. Besides, it could effectively reactivate T cells and reverse the chemoresistance of tumor cells. Therefore, this present study not only provides a novel and promising immune checkpoint blockade inhibitor but also boosts further development of MIPs for cancer immunotherapy. A nanoscale molecularly imprinted polymer (MIP) for blocking the PD-1/PD-L1 axis was rationally developed. The anti-PD-1 nanoMIP was able to effectively block PD-1/PD-L1 interaction, reactivate T cells and reverse the chemoresistance of tumor cells.
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DOI：
10.1038/nrc3239
发表时间：
2012-03-22
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Pardoll DM
通讯作者：
Pardoll DM
影响因子：
158.5
作者：
Robert, Caroline;Schachter, Jacob;Ribas, Antoni
通讯作者：
Ribas, Antoni
影响因子：
15
作者：
Hoshino, Yu;Koide, Hiroyuki;Urakami, Takeo;Kanazawa, Hiroaki;Kodama, Takashi;Oku, Naoto;Shea, Kenneth J.
通讯作者：
Shea, Kenneth J.
影响因子：
64.8
作者：
Mellman, Ira;Coukos, George;Dranoff, Glenn
通讯作者：
Dranoff, Glenn
影响因子：
16.6
作者：
Nishino, H;Huang, CS;Shea, KJ
通讯作者：
Shea, KJ