Improving cancer immunotherapy via co-delivering checkpoint blockade and thrombospondin-1 downregulator.
Improving cancer immunotherapy via co-delivering checkpoint blockade and thrombospondin-1 downregulator.
复制标题
通过共同提供检查点阻断和血小板反应蛋白-1 下调剂改善癌症免疫治疗
DOI：
10.1016/j.apsb.2022.07.012
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发表时间：
2023-08
影响因子：
14.5
通讯作者：
He, Wei
中科院分区：
文献类型：
--
作者：
Xiao, Qingqing;Li, Xiaotong;Liu, Chang;Jiang, Yuxin;He, Yonglong;Zhang, Wanting;Azevedo, Helena S.;Wu, Wei;Xia, Yuanzheng;He, Wei
关键词：
尽管在抗肿瘤免疫治疗方面取得了相当大的成功，但由于疗效有限，检查点阻断抗体在几种恶性肿瘤中的使用仍然受到限制。癌细胞对免疫破坏的不良反应是检查点治疗失败的重要原因。我们假设检查点疗法与天然化学增敏剂相结合可以增强免疫反应。在此，靶向二萜衍生物与检查点阻断（抗 CTLA-4）相结合，以改善使用热敏脂质体作为载体的免疫治疗。在体内，脂质体能够将两种药物有效负载共同递送到肿瘤中。因此，调节性T细胞增殖受到抑制，细胞毒性T细胞浸润增强，实现了深远的免疫治疗效果。此外，另一种临床使用的检查点抗体抗PD-1的免疫治疗效果也受益于二萜衍生物。值得注意的是，我们的机制研究表明，靶向二萜衍生物通过 THBS1 下调以及由此导致的 THBS1-CD47 相互作用的破坏，增加了癌细胞对免疫攻击的敏感性。总的来说，共同提供 THBS1 抑制剂和检查点阻断有望促进癌症免疫治疗。我们首次发现THBS1抑制可以加强检查点治疗。
The use of checkpoint-blockade antibodies is still restricted in several malignancies due to the modest efficacy, despite considerable success in anti-tumor immunotherapy. The poor response of cancer cells to immune destruction is an essential contributor to the failure of checkpoint therapy. We hypothesized that combining checkpoint therapy with natural-product chemosensitizer could enhance immune response. Herein, a targeted diterpenoid derivative was integrated with the checkpoint blockade (anti-CTLA-4) to improve immunotherapy using thermosensitive liposomes as carriers. In vivo, the liposomes enabled the co-delivery of the two drug payloads into the tumor. Consequently, the regulatory T cell proliferation was restrained, the cytotoxic T cell infiltration was enhanced, and the profound immunotherapeutic effect was achieved. In addition, the immunotherapeutic effect of another clinically used checkpoint antibody, anti-PD-1, also benefited from the diterpenoid derivative. Of note, our mechanism study revealed that the targeted diterpenoid derivative increased the sensitivity of cancer cells to immune attack via THBS1 downregulation and the resultant destruction of THBS1-CD47 interaction. Collectively, co-delivering THBS1 inhibitor and checkpoint blockade is promising to boost cancer immunotherapy. We first time discovered that THBS1 suppression could strengthen checkpoint therapy.
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DOI：
10.1038/s41577-019-0269-6
发表时间：
2020-05
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Irvine DJ;Dane EL
通讯作者：
Dane EL
影响因子：
2.7
作者：
Li, Sirui;Shi, Dan;Cheng, Guanghui
通讯作者：
Cheng, Guanghui
纳米碗支持的脂质体改善药物装载和递送
影响因子：
10.8
作者：
Chen, Zhong-Jian;Yang, Si-Cong;Fang, Chao
通讯作者：
Fang, Chao
影响因子：
11.2
作者：
Cha HR;Lee JH;Ponnazhagan S
通讯作者：
Ponnazhagan S
影响因子：
82.9
作者：
Jiménez, B;Volpert, OV;Bouck, N
通讯作者：
Bouck, N