PCFM Lab of Ministry of Education, School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou 510275, China.
Department of Minimally Invasive Interventional Radiology, and Laboratory of Interventional Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510275, China.
Sci Adv. 2020 Feb 5;6(6):eaay7785. doi: 10.1126/sciadv.aay7785. eCollection 2020 Feb.
The response to programmed cell death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) blockade in cancer immunotherapy is limited because of multiple immune evasion mechanisms. Here, a previously unknown strategy is proposed to synergize the nuclear factor κB (NF-κB) inhibition and PD-1 blockade for antitumor immunotherapy. A dual pH-sensitive nanocarrier loading curcumin (CUR) and anti-PD-1 monoclonal antibody (aPD-1) may bind to circulating PD-1 T cells and then follow their infiltration into the tumor. Furthermore, the nanodrug bound to PD-1 T cells may be released in the tumor microenvironment, leaving aPD-1 to block PD-1 on T cells and generating a CUR-encapsulated cationic nanodrug that can be easily taken up by tumor cells/tumor associated macrophages (TAMs). Thus, not only the antitumor T cells mediate efficient CUR delivery to tumor but also the efficient CUR delivery promotes the tumor infiltration of antitumor T cells, thereby resulting in effective activation of antitumor immunity.
癌症免疫疗法中程序性细胞死亡蛋白-1（PD-1）/程序性死亡配体-1（PD-L1）阻断的反应受到多种免疫逃逸机制的限制。在这里，提出了一种以前未知的策略，即联合核因子 κB（NF-κB）抑制和 PD-1 阻断用于抗肿瘤免疫治疗。一种双 pH 敏感的纳米载体负载姜黄素（CUR）和抗 PD-1 单克隆抗体（aPD-1）可以与循环 PD-1 T 细胞结合，然后跟随它们渗透到肿瘤中。此外，与 PD-1 T 细胞结合的纳米药物可能在肿瘤微环境中释放，使 aPD-1 阻断 T 细胞上的 PD-1，并产生一种 CUR 包裹的阳离子纳米药物，很容易被肿瘤细胞/肿瘤相关巨噬细胞（TAMs）摄取。因此，不仅抗肿瘤 T 细胞介导有效的 CUR 递送到肿瘤，而且有效的 CUR 递送到肿瘤促进抗肿瘤 T 细胞的浸润，从而导致有效的抗肿瘤免疫的激活。
