OX40L-expressing M1-like macrophage exosomes for cancer immunotherapy

Yongkang Yu; Tingxuan Li; Meitong Ou; Ran Luo; Hongzhong Chen; He Ren; Zimu Li; Jie Sun; Hanjie Zhang; Shaojun Peng; Yanli Zhao; Lin Mei

doi:10.1016/j.jconrel.2023.11.051

OX40L-expressing M1-like macrophage exosomes for cancer immunotherapy

J Control Release. 2024 Jan:365:469-479. doi: 10.1016/j.jconrel.2023.11.051. Epub 2023 Dec 2.

Authors

Yongkang Yu¹, Tingxuan Li², Meitong Ou², Ran Luo², Hongzhong Chen³, He Ren⁴, Zimu Li⁵, Jie Sun³, Hanjie Zhang², Shaojun Peng⁶, Yanli Zhao⁷, Lin Mei⁸

Affiliations

¹ State Key Laboratory of Advanced Medical Materials and Devices, Tianjin Key Laboratory of Biomedical Materials, Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, PR China; Tianjin Institutes of Health Science, Tianjin 301600, PR China; School of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sen University, Shenzhen 518107, PR China.
² State Key Laboratory of Advanced Medical Materials and Devices, Tianjin Key Laboratory of Biomedical Materials, Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, PR China; Tianjin Institutes of Health Science, Tianjin 301600, PR China.
³ School of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sen University, Shenzhen 518107, PR China.
⁴ Shandong Provincial Key Laboratory of Clinical Research for Pancreatic Diseases, Tumor Immunology and Cytotherapy, Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao 266000, PR China.
⁵ School of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sen University, Shenzhen 518107, PR China; School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 21 Nanyang Link, Singapore, 637371, Singapore.
⁶ Zhuhai Institute of Translational Medicine, Zhuhai Precision Medical Center, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai 519000, PR China.
⁷ School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 21 Nanyang Link, Singapore, 637371, Singapore.
⁸ State Key Laboratory of Advanced Medical Materials and Devices, Tianjin Key Laboratory of Biomedical Materials, Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, PR China; Tianjin Institutes of Health Science, Tianjin 301600, PR China; Shandong Provincial Key Laboratory of Clinical Research for Pancreatic Diseases, Tumor Immunology and Cytotherapy, Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao 266000, PR China. Electronic address: meilin@bme.pumc.edu.cn.

PMID: 38040340
DOI: 10.1016/j.jconrel.2023.11.051

Abstract

With only limited clinical patient benefit, focusing on new immune checkpoint pathways could be an important complement to current immune checkpoint drugs. In addition, not only does T cell-mediated adaptive immunity play an important role, but also macrophage-mediated innate immunity, due to its abundant presence in solid tumors. Here, we developed an engineered M1-like macrophage exosome, OX40L M1-exos. OX40L M1-exos can activate the adaptive immunity by activating the OX40/OX40L pathway and can reprogram M2-like tumor-associated macrophages into M1-like macrophages, thereby restoring and enhancing macrophage-mediated innate immunity. Our OX40L M1-exos achieved an effective synergistic effect of innate and adaptive immunity and achieved a potent therapeutic effect in a mouse breast cancer model, effectively inhibiting tumor growth and metastasis. These results suggest that OX40L M1-exos are an attractive therapeutic strategy and may be an important complement to current cancer immunotherapies.

Keywords: Engineered exosomes; Macrophage; OX40/OX40L; Synergistic innate immunity and adaptive immunity; cancer immunotherapy.

MeSH terms

Animals
Exosomes*
Humans
Immunity, Innate
Immunotherapy / methods
Macrophages
Mice
Neoplasms* / therapy