Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices , Soochow University , 199 Ren'ai Road , Suzhou 215123 , Jiangsu P.R. China.
Joint Department of Biomedical Engineering , University of North Carolina at Chapel Hill and North Carolina State University , Raleigh , North Carolina 27695 , United States.
Nano Lett. 2019 Aug 14;19(8):4879-4889. doi: 10.1021/acs.nanolett.9b00584. Epub 2019 Jul 11.
Despite the promising efficacy of immune checkpoint blockade (ICB) in treating many types of cancers, the clinical benefits have often been restricted by the low objective response rates and systemic immune-related adverse events. Here, a bioresponsive ICB treatment is developed based on the reactive oxygen species (ROS)-sensitive protein complex for controlled sequential release of anti- "don't eat me" signal antibody (aCD47) and antiprogrammed cell death protein 1 (aPD1), by leveraging the abundant ROS in the tumor microenvironment (TME). These protein complexes can also act as scavengers of ROS in the TME to reverse the immunosuppressive responses, thereby enhancing antitumor efficacy in vivo. In a melanoma cancer model, the synergistic antitumor efficacy was achieved, which was accompanied by enhanced T cell immune responses together with reduced immunosuppressive responses.
尽管免疫检查点阻断 (ICB) 在治疗多种癌症方面具有很有前景的疗效，但临床获益常常受到客观反应率低和全身免疫相关不良事件的限制。在这里，基于活性氧 (ROS) 敏感蛋白复合物开发了一种生物响应性 ICB 治疗方法，通过利用肿瘤微环境 (TME) 中丰富的 ROS，实现了抗“别吃我”信号抗体 (aCD47) 和抗程序性细胞死亡蛋白 1 (aPD1) 的控制顺序释放。这些蛋白复合物还可以作为 TME 中 ROS 的清除剂，逆转免疫抑制反应，从而增强体内抗肿瘤疗效。在黑色素瘤癌症模型中，实现了协同的抗肿瘤疗效，同时增强了 T 细胞免疫反应，减少了免疫抑制反应。
