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多肽疫苗偶联介孔载体与免疫原性细胞死亡和 PD-L1 阻断协同作用,增强转移性脊柱肿瘤的免疫治疗。

Peptide vaccine-conjugated mesoporous carriers synergize with immunogenic cell death and PD-L1 blockade for amplified immunotherapy of metastatic spinal.

机构信息

Department of Orthopaedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China.

Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China.

出版信息

J Nanobiotechnology. 2021 Aug 12;19(1):243. doi: 10.1186/s12951-021-00975-5.


DOI:10.1186/s12951-021-00975-5
PMID:34384429
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8362242/
Abstract

The clinical treatment of metastatic spinal tumor remains a huge challenge owing to the intrinsic limitations of the existing methods. Programmed cell death protein 1 (PD1)/programmed cell death ligand 1 (PD-L1) pathway blockade has been explored as a promising immunotherapeutic strategy; however, their inhibition has a low response rate, leading to the minimal cytotoxic T cell infiltration. To ameliorate the immunosuppressive microenvironment of intractable tumor and further boost the efficacy of immunotherapy, we report an all-round mesoporous nanocarrier composed of an upconverting nanoparticle core and a large-pore mesoporous silica shell (UCMS) that is simultaneously loaded with photosensitizer molecules, the IDO-derived peptide vaccine AL-9, and PD-L1 inhibitor. The IDO-derived peptide can be recognized by the dendritic cells and presented to CD8 cytotoxic T cells, thereby enhancing the immune response and promoting the killing of the IDO-expressed tumor cells. Meanwhile, the near-infrared (NIR) activated photodynamic therapy (PDT) could induce immunogenic cell death (ICD), which promotes the effector T-cell infiltration. By combining the PDT-elicited ICD, peptide vaccine and immune checkpoint blockade, the designed UCMS@Pep-aPDL1 successfully potentiated local and systemic antitumor immunity and reduced the progression of metastatic foci, demonstrating a synergistic strategy for cancer immunotherapy.

摘要

由于现有方法的固有局限性,转移性脊柱肿瘤的临床治疗仍然是一个巨大的挑战。程序性细胞死亡蛋白 1(PD1)/程序性细胞死亡配体 1(PD-L1)通路阻断已被探索作为一种很有前途的免疫治疗策略;然而,它们的抑制作用反应率低,导致细胞毒性 T 细胞浸润很少。为了改善难治性肿瘤的免疫抑制微环境,并进一步提高免疫治疗的效果,我们报告了一种由上转换纳米颗粒核和大孔介孔二氧化硅壳(UCMS)组成的全方位介孔纳米载体,该载体同时负载光敏剂分子、IDO 衍生肽疫苗 AL-9 和 PD-L1 抑制剂。IDO 衍生肽可被树突状细胞识别并呈递给 CD8 细胞毒性 T 细胞,从而增强免疫反应,促进 IDO 表达肿瘤细胞的杀伤。同时,近红外(NIR)激活的光动力疗法(PDT)可诱导免疫原性细胞死亡(ICD),促进效应 T 细胞浸润。通过结合 PDT 诱导的 ICD、肽疫苗和免疫检查点阻断,设计的 UCMS@Pep-aPDL1 成功增强了局部和全身抗肿瘤免疫,并减少了转移性病灶的进展,为癌症免疫治疗提供了一种协同策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4da2/8362242/07fa6dbaa117/12951_2021_975_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4da2/8362242/bb9329c77a4e/12951_2021_975_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4da2/8362242/3c95d90e3a73/12951_2021_975_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4da2/8362242/747ce1de4a18/12951_2021_975_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4da2/8362242/096ea79091ab/12951_2021_975_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4da2/8362242/5795a1449ba5/12951_2021_975_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4da2/8362242/707e0ae63f12/12951_2021_975_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4da2/8362242/07fa6dbaa117/12951_2021_975_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4da2/8362242/bb9329c77a4e/12951_2021_975_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4da2/8362242/3c95d90e3a73/12951_2021_975_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4da2/8362242/747ce1de4a18/12951_2021_975_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4da2/8362242/096ea79091ab/12951_2021_975_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4da2/8362242/5795a1449ba5/12951_2021_975_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4da2/8362242/707e0ae63f12/12951_2021_975_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4da2/8362242/07fa6dbaa117/12951_2021_975_Fig7_HTML.jpg

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[4]
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[5]
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[6]
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[7]
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本文引用的文献

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