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源自细菌外膜囊泡的个性化癌症疫苗,通过抗体介导可被树突状细胞持续摄取。

Personalized cancer vaccines from bacteria-derived outer membrane vesicles with antibody-mediated persistent uptake by dendritic cells.

作者信息

Liang Jie, Cheng Keman, Li Yao, Xu Jiaqi, Chen Yiwei, Ma Nana, Feng Qingqing, Zhu Fei, Ma Xiaotu, Zhang Tianjiao, Yue Yale, Liu Guangna, Guo Xinjing, Chen Zhiqiang, Wang Xinwei, Zhao Ruifang, Zhao Ying, Shi Jian, Zhao Xiao, Nie Guangjun

机构信息

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China.

Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China.

出版信息

Fundam Res. 2021 Dec 22;2(1):23-36. doi: 10.1016/j.fmre.2021.11.032. eCollection 2022 Jan.


DOI:10.1016/j.fmre.2021.11.032
PMID:38933907
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11197747/
Abstract

Nanocarriers with intrinsic immune adjuvant properties can activate the innate immune system while delivering tumor antigen, thus efficiently facilitating antitumor adaptive immunity. Bacteria-derived outer membrane vesicles (OMVs) are an excellent candidate due to their abundance of pathogen associated molecular patterns. However, during the uptake of OMVs by dendritic cells (DCs), the interaction between lipopolysaccharide and toll-like receptor 4 induces rapid DC maturation and uptake blockage, a phenomenon we refer to as "maturation-induced uptake obstruction" (MUO). Herein we decorated OMV with the DC-targeting αDEC205 antibody (OMV-DEC), which endowed the nanovaccine with an uptake mechanism termed as "not restricted to maturation via antibody modifying" (Normandy), thereby overcoming the MUO phenomenon. We also proved the applicability of this nanovaccine in identifying the human tumor neoantigens through rapid antigen display. In summary, this engineered OMV represents a powerful nanocarrier for personalized cancer vaccines, and this antibody modification strategy provides a reference to remodel the DC uptake pattern in nanocarrier design.

摘要

具有内在免疫佐剂特性的纳米载体在递送肿瘤抗原时可激活先天免疫系统,从而有效地促进抗肿瘤适应性免疫。细菌衍生的外膜囊泡(OMV)因其富含病原体相关分子模式而成为极佳的选择。然而,在树突状细胞(DC)摄取OMV的过程中,脂多糖与Toll样受体4之间的相互作用会诱导DC迅速成熟并导致摄取受阻,我们将这种现象称为“成熟诱导摄取阻塞”(MUO)。在此,我们用靶向DC的αDEC205抗体(OMV-DEC)修饰OMV,赋予了这种纳米疫苗一种称为“抗体修饰介导的非成熟限制摄取”(诺曼底)的摄取机制,从而克服了MUO现象。我们还证明了这种纳米疫苗在通过快速抗原展示识别人类肿瘤新抗原方面的适用性。总之,这种工程化的OMV代表了一种用于个性化癌症疫苗的强大纳米载体,这种抗体修饰策略为在纳米载体设计中重塑DC摄取模式提供了参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dc6/11197747/61fc3a5dcd0a/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dc6/11197747/271b44c9f14a/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dc6/11197747/c9809f7ade7a/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dc6/11197747/2c6855773e9b/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dc6/11197747/2a6d644622d9/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dc6/11197747/1aac2d3264cd/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dc6/11197747/a50b63b06506/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dc6/11197747/45868e8b9634/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dc6/11197747/61fc3a5dcd0a/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dc6/11197747/271b44c9f14a/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dc6/11197747/c9809f7ade7a/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dc6/11197747/2c6855773e9b/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dc6/11197747/2a6d644622d9/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dc6/11197747/1aac2d3264cd/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dc6/11197747/a50b63b06506/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dc6/11197747/45868e8b9634/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dc6/11197747/61fc3a5dcd0a/gr7.jpg

相似文献

[1]
Personalized cancer vaccines from bacteria-derived outer membrane vesicles with antibody-mediated persistent uptake by dendritic cells.

Fundam Res. 2021-12-22

[2]
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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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引用本文的文献

[1]
United under stress: High-speed transport network emerging at bacterial living edge.

Fundam Res. 2022-5-14

[2]
Advances in Engineered Macrophages: A New Frontier in Cancer Immunotherapy.

Cell Death Dis. 2024-4-1

[3]
Bacteria and Bacterial Components as Natural Bio-Nanocarriers for Drug and Gene Delivery Systems in Cancer Therapy.

Pharmaceutics. 2023-10-19

[4]
mRNA Delivery Platform Based on Bacterial Outer Membrane Vesicles for Tumor Vaccine.

Bio Protoc. 2023-7-5

[5]
Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy.

Nat Rev Clin Oncol. 2023-9

[6]
Bacterial extracellular vesicles-based therapeutic strategies for bone and soft tissue tumors therapy.

Theranostics. 2022

[7]
Bacterial outer membrane vesicle-based cancer nanovaccines.

Cancer Biol Med. 2022-9-23

本文引用的文献

[1]
Multifunctional biomolecule nanostructures for cancer therapy.

Nat Rev Mater. 2021

[2]
Bioengineered bacteria-derived outer membrane vesicles as a versatile antigen display platform for tumor vaccination via Plug-and-Display technology.

Nat Commun. 2021-4-6

[3]
Therapeutic Targeting of the Tumor Microenvironment.

Cancer Discov. 2021-4

[4]
Overcoming Resistance to Tumor-Targeted and Immune-Targeted Therapies.

Cancer Discov. 2021-4

[5]
Personalized cancer vaccine strategy elicits polyfunctional T cells and demonstrates clinical benefits in ovarian cancer.

NPJ Vaccines. 2021-3-15

[6]
Targeting a neoantigen derived from a common mutation.

Science. 2021-3-5

[7]
High-dose per Fraction Radiotherapy Induces Both Antitumor Immunity and Immunosuppressive Responses in Prostate Tumors.

Clin Cancer Res. 2021-3-1

[8]
Biomineralized Bacterial Outer Membrane Vesicles Potentiate Safe and Efficient Tumor Microenvironment Reprogramming for Anticancer Therapy.

Adv Mater. 2020-11

[9]
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Nat Rev Immunol. 2020-5-20

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Efficacy of immunotherapy targeting the neoantigen derived from epidermal growth factor receptor T790M/C797S mutation in non-small cell lung cancer.

Cancer Sci. 2020-6-18

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