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Anti-tumor immunotherapy using engineered bacterial outer membrane vesicles fused to lysosome-targeting chimeras mediated by transferrin receptor

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机构： [1]College of Food Science and Technology, Yunnan Agricultural University, No. 452 Fengyuan Road, Kunming 650000, China [2]Yunnan Provincial Key Laboratory of Precision Nutrition and Personalized Food Manufacturing, Yunnan Agricultural University, Kunming 650000, China [3]Department of Cardiovascular Surgery, The First People Hospital of Yunnan Province, Xishan District, No.157 Jinbi Road, Kunming 650032, China [4]Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA [5]CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, 11 Beiyitiao, Zhongguancun, Beijing 100190, China [6]Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China

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The lysosome-targeting chimera (LYTAC) approach has shown promise for the targeted degradation of secreted and membrane proteins via lysosomes. However, there have been challenges in design, development, and targeting. Here, we have designed a genetically engineered transferrin receptor (TfR)-mediated lysosome-targeting chimera (TfR-LYTAC) that is efficiently internalized via TfR-mediate endocytosis and targets PD-L1 for lysosomal degradation in cultured cells but not in vivo due to short half-life and poor tumor targeting. A delivery platform was developed by fusing TfR-LYTAC to the surface of bacterial outer membrane vesicles (OMVs). The engineered OMV-LYTAC combines PD-1/PD-L1 pathway inhibition with LYTAC and immune activation by bacterial OMVs. OMV-LYTAC significantly reduced tumor growth in vivo. We have provided a modular and simple genetic strategy for lysosomal degradation as well as a delivery platform for in vivo tumor targeting. The study paves the way for the targeting and degradation of extracellular proteins using the TfR-LYTAC system.Copyright © 2024 Elsevier Ltd. All rights reserved.

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最新[2023]版：

大类 | 1 区生物学

小类 | 2 区生化与分子生物学

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出版当年[2023]版：

Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

最新[2023]版：

Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

影响因子： 6.6 最新[2023版] 8.2 最新五年平均 6.6 出版当年[2023版] 8.2 出版当年五年平均 8.6 出版前一年[2022版]

第一作者：

第一作者机构： [1]College of Food Science and Technology, Yunnan Agricultural University, No. 452 Fengyuan Road, Kunming 650000, China [2]Yunnan Provincial Key Laboratory of Precision Nutrition and Personalized Food Manufacturing, Yunnan Agricultural University, Kunming 650000, China

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通讯作者：

通讯机构： [1]College of Food Science and Technology, Yunnan Agricultural University, No. 452 Fengyuan Road, Kunming 650000, China [2]Yunnan Provincial Key Laboratory of Precision Nutrition and Personalized Food Manufacturing, Yunnan Agricultural University, Kunming 650000, China [5]CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, 11 Beiyitiao, Zhongguancun, Beijing 100190, China [6]Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China

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