Functional nanovesicles displaying anti-PD-L1 antibodies for programmed photoimmunotherapy

被引:28
作者
Chen, Hu [1 ,2 ]
Zhang, Pengfei [1 ,2 ,3 ]
Shi, Yesi [1 ,2 ]
Liu, Chao [1 ,2 ]
Zhou, Qianqian [4 ]
Zeng, Yun [1 ,2 ]
Cheng, Hongwei [1 ,2 ]
Dai, Qixuan [1 ,2 ]
Gao, Xing [1 ,2 ]
Wang, Xiaoyong [1 ,2 ]
Liu, Gang [1 ,2 ]
机构
[1] Xiamen Univ, State Key Lab Mol Vaccinol & Mol Diagnost, Sch Publ Hlth, Xiamen 361102, Peoples R China
[2] Xiamen Univ, Ctr Mol Imaging & Translat Med, Sch Publ Hlth, Xiamen 361102, Peoples R China
[3] Southern Med Univ, Sch Lab Med & Biotechnol, Inst Mol Immunol, Guangzhou 510080, Peoples R China
[4] Shanghai Jiao Tong Univ, Tongren Hosp, Sch Med, Shanghai 200336, Peoples R China
基金
中国国家自然科学基金; 中国博士后科学基金;
关键词
Photoimmunotherapy; Anti-PD-L1; antibodies; Targeting delivery; Nanovesicles; CROSS-PRESENTATION; CANCER; IMMUNOTHERAPY; LYMPHOCYTES; DELIVERY; BLOCKADE; PD-L1; CELLS;
D O I
10.1186/s12951-022-01266-3
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Background: Photoimmunotherapy is one of the most promising strategies in tumor immunotherapies, but targeted delivery of photosensitizers and adjuvants to tumors remains a major challenge. Here, as a proof of concept, we describe bone marrow mesenchymal stem cell-derived nanovesicles (NVs) displaying anti-PD-L1 antibodies (aPD-L1) that were genetically engineered for targeted drug delivery. Results: The high affinity and specificity between aPD-L1 and tumor cells allow aPD-L1 NVs to selectively deliver photosensitizers to cancer tissues and exert potent directed photothermal ablation. The tumor immune microenvironment was programmed via ablation, and the model antigen ovalbumin (OVA) was designed to fuse with aPD-L1. The corresponding membrane vesicles were then extracted as an antigen-antibody integrator (AAI). AAI can work as a nanovaccine with the immune adjuvant R837 encapsulated. This in turn can directly stimulate dendritic cells (DCs) to boast the body's immune response to residual lesions. Conclusions: aPD-L1 NV-based photoimmunotherapy significantly improves the efficacy of photothermal ablation and synergistically enhances subsequent immune activation. This study describes a promising strategy for developing ligand-targeted and personalized cancer photoimmunotherapy.
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页数:15
相关论文
共 48 条
[1]   Therapeutic Targeting of checkpoint Receptors within the DnAM1 Axis [J].
Alteber, Zoya ;
Kotturi, Maya F. ;
Whelan, Sarah ;
Ganguly, Sudipto ;
Weyl, Emmanuel ;
Pardoll, Drew M. ;
Hunter, John ;
Ophir, Eran .
CANCER DISCOVERY, 2021, 11 (05) :1040-1051
[2]   PD-L1 Blockade Therapy: Location, Location, Location [J].
Brown, Chrysothemis C. ;
Wolchok, Jedd D. .
CANCER CELL, 2020, 38 (05) :615-617
[3]   Treatment of metastatic uveal melanoma with adoptive transfer of tumour-infiltrating lymphocytes: a single-centre, two-stage, single-arm, phase 2 study [J].
Chandran, Smita S. ;
Somerville, Robert P. T. ;
Yang, James C. ;
Sherry, Richard M. ;
Klebanoff, Christopher A. ;
Goff, Stephanie L. ;
Wunderlich, John R. ;
Danforth, David N. ;
Zlott, Daniel ;
Paria, Biman C. ;
Sabesan, Arvind C. ;
Srivastava, Abhishek K. ;
Xi, Liqiang ;
Pham, Trinh H. ;
Raffeld, Mark ;
White, Donald E. ;
Toomey, Mary Ann ;
Rosenberg, Steven A. ;
Kammula, Udai S. .
LANCET ONCOLOGY, 2017, 18 (06) :792-802
[4]   Oncology Meets Immunology: The Cancer-Immunity Cycle [J].
Chen, Daniel S. ;
Mellman, Ira .
IMMUNITY, 2013, 39 (01) :1-10
[5]   Bioinspired and Biomimetic Nanomedicines [J].
Chen, Zhaowei ;
Wang, Zejun ;
Gu, Zhen .
ACCOUNTS OF CHEMICAL RESEARCH, 2019, 52 (05) :1255-1264
[6]   Targeting Programmed Cell Death-1 (PD-1) and Ligand (PD-L1): A new era in cancer active immunotherapy [J].
Constantinidou, Anastasia ;
Alifieris, Constantinos ;
Trafalis, Dimitrios T. .
PHARMACOLOGY & THERAPEUTICS, 2019, 194 :84-106
[7]   Tumour antigens recognized by T lymphocytes: at the core of cancer immunotherapy [J].
Coulie, Pierre G. ;
Van den Eynde, Benoit J. ;
van der Bruggen, Pierre ;
Boon, Thierry .
NATURE REVIEWS CANCER, 2014, 14 (02) :135-146
[8]   Cancer Immunotherapy [J].
Couzin-Frankel, Jennifer .
SCIENCE, 2013, 342 (6165) :1432-1433
[9]   Drug Delivery with Extracellular Vesicles: From Imagination to Innovation [J].
de Jong, Olivier G. ;
Kooijmans, Sander A. A. ;
Murphy, Daniel E. ;
Jiang, Linglei ;
Evers, Martijn J. W. ;
Sluijter, Joost P. G. ;
Vader, Pieter ;
Schiffelers, Raymond M. .
ACCOUNTS OF CHEMICAL RESEARCH, 2019, 52 (07) :1761-1770
[10]   Designed proteins assemble antibodies into modular nanocages [J].
Divine, Robby ;
Dang, Ha, V ;
Ueda, George ;
Fallas, Jorge A. ;
Vulovic, Ivan ;
Sheffler, William ;
Saini, Shally ;
Zhao, Yan Ting ;
Raj, Infencia Xavier ;
Morawski, Peter A. ;
Jennewein, Madeleine F. ;
Homad, Leah J. ;
Wan, Yu-Hsin ;
Tooley, Marti R. ;
Seeger, Franziska ;
Etemadi, Ali ;
Fahning, Mitchell L. ;
Lazarovits, James ;
Roederer, Alex ;
Walls, Alexandra C. ;
Stewart, Lance ;
Mazloomi, Mohammadali ;
King, Neil P. ;
Campbell, Daniel J. ;
McGuire, Andrew T. ;
Stamatatos, Leonidas ;
Ruohola-Baker, Hannele ;
Mathieu, Julie ;
Veesler, David ;
Baker, David .
SCIENCE, 2021, 372 (6537) :47-+