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Engineered extracellular vesicles for concurrent Anti-PDL1 immunotherapy and chemotherapy.

作者信息

Chen Yundi, Wang Lixue, Zheng Mingfeng, Zhu Chuandong, Wang Guosheng, Xia Yiqiu, Blumenthal Ethan J, Mao Wenjun, Wan Yuan

机构信息

The Pq Laboratory of Micro/Nano BiomeDx, Department of Biomedical Engineering, Binghamton University-SUNY, Binghamton, NY, 13902, United States.

Department of Radiotherapy, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210003, China.

出版信息

Bioact Mater. 2021 Jul 21;9:251-265. doi: 10.1016/j.bioactmat.2021.07.012. eCollection 2022 Mar.


DOI:10.1016/j.bioactmat.2021.07.012
PMID:34820569
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8586263/
Abstract

Immune checkpoint inhibitors (ICI) targeting PD-1/PD-L1 have been approved for the treatment of a variety of cancers. However, the efficacy of antibody-based ICIs could be further improved by mitigating anti-drug antibodies, proteolytic cleavage, and on-target off-tumor toxicity. One strategy for accomplishing this is through the use of extracellular vesicles (EVs), cell derived submicron vesicles with many unique properties. We constructed an engineered MDA-MB-231 cell line for harvesting EVs. This was accomplished by overexpressing a high-affinity variant human PD-1 protein (havPD-1), while simultaneously knocking out intrinsic PD-L1 and beta-2 microglobulin. The engineered havPD-1 EVs reduced PD-L1 overexpressing cancer cell proliferation and induced cellular apoptosis. Moreover, the EVs were shown to efficiently block PD-L1 mediated T cell suppression. Meanwhile antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity were not observed. The havPD-1 EVs treatment resulted in robust anti-tumor activity in both preventative co-implantation and therapeutic xenograft tumor models reconstituted with human T cells. The efficacy of the havPD-1 EVs was shown to be comparable to clinical anti-PD1 monoclonal antibodies. Additionally, loading the havPD-1 EVs with a potent PARP inhibitor was shown to further augment treatment efficacy. In brief, the engineered universal EVs harboring havPD-1 proteins can be used for cancer concurrent immunotherapy and chemotherapy.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdfd/8586263/72bdae8ce30f/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdfd/8586263/ca5e25dcd92d/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdfd/8586263/8e73ce712b93/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdfd/8586263/94556f5afa00/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdfd/8586263/0f48cf8ef798/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdfd/8586263/d4788d0fd58d/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdfd/8586263/cb84c8250963/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdfd/8586263/72bdae8ce30f/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdfd/8586263/ca5e25dcd92d/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdfd/8586263/8e73ce712b93/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdfd/8586263/94556f5afa00/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdfd/8586263/0f48cf8ef798/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdfd/8586263/d4788d0fd58d/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdfd/8586263/cb84c8250963/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdfd/8586263/72bdae8ce30f/gr6.jpg

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[1]
Engineered extracellular vesicles for concurrent Anti-PDL1 immunotherapy and chemotherapy.

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[2]
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[3]
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[4]
Harnessing engineered extracellular vesicles for enhanced therapeutic efficacy: advancements in cancer immunotherapy.

J Exp Clin Cancer Res. 2025-5-2

[5]
Role of Triple-Negative Breast Cancer-Derived Extracellular Vesicles in Metastasis: Implications for Therapeutics and Biomarker Development.

J Cell Mol Med. 2025-3

[6]
Natural and Bioengineered Extracellular Vesicles in Diagnosis, Monitoring and Treatment of Cancer.

ACS Nano. 2025-2-18

[7]
Ultrasonication outperforms electroporation for extracellular vesicle cargo depletion.

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[8]
Strategies for Small Extracellular Vesicle-Based Cancer Immunotherapy.

Research (Wash D C). 2024-7-22

[9]
Extracellular vesicles in cancer: golden goose or Trojan horse.

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[10]
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本文引用的文献

[1]
PD-L1 degradation pathway and immunotherapy for cancer.

Cell Death Dis. 2020-11-6

[2]
Conferring receptors on recipient cells with extracellular vesicles for targeted drug delivery.

Bioact Mater. 2020-9-24

[3]
Therapeutic plasma exchange clears circulating soluble PD-L1 and PD-L1-positive extracellular vesicles.

J Immunother Cancer. 2020-8

[4]
Factors influencing the measurement of the secretion rate of extracellular vesicles.

Analyst. 2020-8-24

[5]
An Avidity-Based PD-L1 Antagonist Using Nanoparticle-Antibody Conjugates for Enhanced Immunotherapy.

Nano Lett. 2020-7-8

[6]
Tumor cell-derived exosomes home to their cells of origin and can be used as Trojan horses to deliver cancer drugs.

Theranostics. 2020

[7]
Tumor-derived exosomes in the regulation of macrophage polarization.

Inflamm Res. 2020-3-11

[8]
Tumor cell-intrinsic PD-1 receptor is a tumor suppressor and mediates resistance to PD-1 blockade therapy.

Proc Natl Acad Sci U S A. 2020-3-11

[9]
The Proteolytic Cleavage of Therapeutic Monoclonal Antibody Hinge Region: More Than a Matter of Subclass.

Front Immunol. 2020

[10]
The Intracellular Delivery Of Anti-HPV16 E7 scFvs Through Engineered Extracellular Vesicles Inhibits The Proliferation Of HPV-Infected Cells.

Int J Nanomedicine. 2019-11-7

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