Department of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiangxi Rd, Guangzhou 510120, Guangdong Province, China.
Nanoscale. 2019 Apr 23;11(16):7996-8011. doi: 10.1039/c9nr01434a.
Despite the functions of anti-PD-1 antibodies as immune checkpoint regulators, less than 30% of patients exhibit durable therapeutic responses to anti-PD-1 antibodies. Studies have shown that insufficient infiltration of immune cells might limit the outcome of anti-PD-1 therapy. Therefore, we synthesized an immune cell-recruiting liposomal system (FN-nps) to improve this therapeutic strategy. The FN-nps could generate cell debris and expose heat shock protein 70, which could recruit immune cells to tumor sites to assist in anti-PD-1 treatment. In vivo experiments revealed that the FN-nps could assist in anti-PD-1 therapy by increasing the number of lymphocytes in the peripheral blood and tumor site by generating tumor antigens, and this effect was accompanied by an increase in cytokine expression. The number of CTLs increased and mRNA expression levels of cytokines were regulated when the FN-nps were combined with anti-PD-1 therapy. The revealed properties of the liposomal system make it highly promising for assisting in anti-PD-1 antibody immunotherapy in different cancers.
尽管抗 PD-1 抗体具有免疫检查点调节剂的作用，但只有不到 30%的患者对抗 PD-1 抗体表现出持久的治疗反应。研究表明，免疫细胞的浸润不足可能限制抗 PD-1 治疗的效果。因此，我们合成了一种免疫细胞募集脂质体系统（FN-nps）来改进这种治疗策略。FN-nps 可以产生细胞碎片并暴露热休克蛋白 70，从而招募免疫细胞到肿瘤部位，以协助抗 PD-1 治疗。体内实验表明，FN-nps 可以通过产生肿瘤抗原来增加外周血和肿瘤部位的淋巴细胞数量，从而协助抗 PD-1 治疗，同时伴随着细胞因子表达的增加。当 FN-nps 与抗 PD-1 治疗联合使用时，CTL 的数量增加，细胞因子的 mRNA 表达水平也得到调节。脂质体系统的这些特性使其在不同癌症的抗 PD-1 抗体免疫治疗中具有很大的应用前景。
