Wu Jiayan, Chen Jie, Feng Yuanji, Zhang Sijia, Lin Lin, Guo Zhaopei, Sun Pingjie, Xu Caina, Tian Huayu, Chen Xuesi
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
University of Science and Technology of China, Hefei 230026, China.
Sci Adv. 2020 Sep 30;6(40). doi: 10.1126/sciadv.abc7828. Print 2020 Sep.
Immune checkpoint blockade therapy (ICT) has shown potential in the treatment of multiple tumors, but suffers poor response rate in clinic. We found that even combining ICT with chemotherapy, which was wildly used in clinical trials, failed to achieve satisfactory tumor inhibition in the B16F10 model. Thus, we further constructed a previously unexplored immune cocktail therapy and realized multiple boosting of the cancer-immunity cycle. Cocktail therapy consisted of two kinds of tumor microenvironment-responsive drug and gene delivery nanoparticles to achieve specific delivery of doxorubicin and codelivery of plasmids expressed small hairpin RNA of PD-L1 (pshPD-L1) and hyaluronidase (pSpam1) in the tumor area. Experimental evidences proved that any component in the cocktail therapy was indispensable, and the cocktail therapy exhibited excellent antitumor effects against different types of tumors. The cocktail therapy presented here offers a searching strategy for more synergistic units with ICT and is meaningful for developing more efficient antitumor immunotherapy.
免疫检查点阻断疗法（ICT）在多种肿瘤的治疗中显示出潜力，但在临床上的应答率较低。我们发现，即使将ICT与在临床试验中广泛使用的化疗相结合，在B16F10模型中也未能实现令人满意的肿瘤抑制效果。因此，我们进一步构建了一种此前未被探索的免疫鸡尾酒疗法，并实现了癌症免疫循环的多重增强。鸡尾酒疗法由两种肿瘤微环境响应性药物和基因递送纳米颗粒组成，以实现阿霉素在肿瘤区域的特异性递送以及共递送表达PD-L1小发夹RNA（pshPD-L1）和透明质酸酶（pSpam1）的质粒。实验证据证明，鸡尾酒疗法中的任何成分都是不可或缺的，并且该鸡尾酒疗法对不同类型的肿瘤均表现出优异的抗肿瘤效果。本文介绍的鸡尾酒疗法为与ICT形成更多协同单元提供了一种探索策略，对于开发更有效的抗肿瘤免疫疗法具有重要意义。
