超声辐照靶向微泡联合 PD-1 抑制剂增强 B 细胞淋巴瘤的抗肿瘤活性。
Targeted microbubbles with ultrasound irradiation and PD-1 inhibitor to increase antitumor activity in B-cell lymphoma.
机构信息
Department of Oncology, Zhongda Hospital, Medical School, Southeast University, Nanjing 210009, China.
Department of Oncology, Jiangsu Cancer Hospital, Nanjing 210009, China.
出版信息
Nanomedicine (Lond). 2018 Feb;13(3):297-311. doi: 10.2217/nnm-2017-0296. Epub 2018 Jan 17.
AIM
Severe cardiac toxicity of doxorubicin and an immunosuppressive tumor micro-environment become main obstacles for the effective treatment of B-cell lymphoma. In this research, rituximab-conjugated and doxorubicin-loaded microbubbles (RDMs) were designed for exploring a combination approach of targeted microbubbles with ultrasound (US) irradiation and PD-1 inhibitor to overcome obstacles mentioned above.
METHODS
In vivo studies were performed on SU-DHL-4 cell-grafted mice and ex vivo studies were performed on CD20 human SU-DHL-4 cells and human T cells.
RESULTS
A greater therapeutic effect and higher expression of PD-L1 protein expression were obtained with RDMs with US irradiation in vivo. A significant inhibitory effect on SU-DHL-4 B-cell lymphoma cells was observed after treated by RDMs with US irradiation and PD-1 inhibitor ex vivo.
CONCLUSION
Combination of RDMs with US irradiation and PD-1 inhibitor could be a promising therapeutic strategy for B-cell lymphoma.
目的
阿霉素的严重心脏毒性和免疫抑制性肿瘤微环境成为 B 细胞淋巴瘤有效治疗的主要障碍。在这项研究中，设计了利妥昔单抗偶联和阿霉素负载的微泡（RDMs），以探索靶向微泡联合超声（US）照射和 PD-1 抑制剂的组合方法，以克服上述障碍。
方法
在 SU-DHL-4 细胞移植小鼠中进行体内研究，并在 CD20 人 SU-DHL-4 细胞和人 T 细胞上进行体外研究。
结果
在体内，用超声照射的 RDMs 可获得更好的治疗效果和更高的 PD-L1 蛋白表达。用超声照射的 RDMs 和 PD-1 抑制剂处理后，体外观察到对 SU-DHL-4 B 细胞淋巴瘤细胞的显著抑制作用。
结论
RDMs 联合 US 照射和 PD-1 抑制剂可能是治疗 B 细胞淋巴瘤的一种很有前途的治疗策略。
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