State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Screening, Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, No. 639 Longmian Avenue, Jiangning District, Nanjing, 211198, China.
Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, 130117, China.
J Nanobiotechnology. 2021 Dec 20;19(1):434. doi: 10.1186/s12951-021-01193-9.
As an efficient tumor immunotherapy, PD-1 antibody has been gradually used in clinical tumor treatment, but the low response rate and excessive immune response limit its extensive application.
Herein, a therapeutic regime for the reinvigoration and activation of the tumor immune microenvironment is introduced to improve the anti-tumor effect of the PD-1 antibody. To comprehensively improve the effect of the immunotherapy and reduce excessive immune response, a biomimetic cascade targeting nanosystem, siRNA@PLOV, which was fused by photothermal sensitive liposomes (PTSLs) and attenuated Salmonella outer membrane vesicles (OMVs), was administered in the tumor therapy for targeting of tumor tissues and T cells within tumor respectively. The fused PLOVs which not only retained the biological character of the OMVs, but also enhanced the drug loading ability. The results demonstrated that the immunogenicity of OMVs and photothermal effects can obviously increase the infiltration of T cells and the silencing of CD38 can effectively improve the T cell cytotoxicity, especially combining with PD-1 antibody.
Interesting, this study revealed that anti-PD-1 administration on the 5th day after siRNA@PLOV treatment had the best performance in killing tumors compared with other groups. In addition, this new therapeutic regime also presents a novel strategy for inducing "vaccine effects", conclusively highlighting its potential in preventing tumor recurrence and improving prognosis.
作为一种有效的肿瘤免疫疗法，PD-1 抗体已逐渐应用于临床肿瘤治疗，但低反应率和过度免疫反应限制了其广泛应用。
本文介绍了一种肿瘤免疫微环境的再激活和激活治疗方案，以提高 PD-1 抗体的抗肿瘤效果。为了全面提高免疫治疗效果，减少过度免疫反应，构建了一种仿生级联靶向纳米系统 siRNA@PLOV，它由光热敏感脂质体（PTSLs）和减毒沙门氏菌外膜囊泡（OMVs）融合而成，分别靶向肿瘤组织和肿瘤内 T 细胞。融合的 PLOV 不仅保留了 OMV 的生物学特性，而且增强了药物载药能力。结果表明，OMVs 的免疫原性和光热效应能明显增加 T 细胞的浸润，CD38 的沉默能有效提高 T 细胞的细胞毒性，尤其是与 PD-1 抗体联合使用时。
有趣的是，这项研究表明，与其他组相比，在 siRNA@PLOV 治疗后第 5 天给予抗 PD-1 治疗在杀伤肿瘤方面表现最佳。此外，这种新的治疗方案还为诱导“疫苗效应”提供了一种新策略，突出了其在预防肿瘤复发和改善预后方面的潜力。
