Engineering of dendritic cell bispecific extracellular vesicles for tumor-targeting immunotherapy
Fang Xu,
Dongpeng Jiang,
Jialu Xu,
Huaxing Dai,
Qin Fan,
Ziying Fei,
Beilei Wang,
Yue Zhang,
Qingle Ma,
Qianyu Yang,
Yitong Chen,
Edikan A. Ogunnaike,
Jianhong Chu,
Chao Wang
Affiliations
Fang Xu
Laboratory for Biomaterial and Immunoengineering, Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu 215123, China
Dongpeng Jiang
Institute of Blood and Marrow Transplantation, National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu 215123, China
Jialu Xu
Laboratory for Biomaterial and Immunoengineering, Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu 215123, China
Huaxing Dai
Laboratory for Biomaterial and Immunoengineering, Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu 215123, China
Qin Fan
Institute of Advanced Materials (IAM) and School of Materials Science and Engineering, Nanjing University of Posts & Telecommunications, Nanjing 210000, China
Ziying Fei
Laboratory for Biomaterial and Immunoengineering, Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu 215123, China
Beilei Wang
Laboratory for Biomaterial and Immunoengineering, Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu 215123, China
Yue Zhang
Laboratory for Biomaterial and Immunoengineering, Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu 215123, China
Qingle Ma
Laboratory for Biomaterial and Immunoengineering, Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu 215123, China
Qianyu Yang
Laboratory for Biomaterial and Immunoengineering, Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu 215123, China
Yitong Chen
Laboratory for Biomaterial and Immunoengineering, Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu 215123, China
Edikan A. Ogunnaike
Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA
Jianhong Chu
Institute of Blood and Marrow Transplantation, National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu 215123, China; Corresponding author
Chao Wang
Laboratory for Biomaterial and Immunoengineering, Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu 215123, China; Corresponding author
Summary: Advances in the development of therapeutic extracellular vesicles (EVs) for cancer immunotherapy have allowed them to emerge as an alternative to cell therapy. In this proof-of-concept work, we develop bispecific EVs (BsEVs) by genetically engineering EV-producing dendritic cells (DCs) with aCD19 scFv and PD1 for targeting tumor antigens and blocking immune checkpoint proteins simultaneously. We find that these bispecific EVs (EVs-PD1-aCD19) have an impressive ability to accumulate in huCD19-expressing solid tumors following intravenous injection. In addition, EVs-PD1-aCD19 can remarkably reverse the immune landscape of the solid tumor by blocking PD-L1. Furthermore, EVs-PD1-aCD19 can also target tumor-derived EVs in circulation, which prevents the formation of a premetastatic niche in other tissues. Our technology is a demonstration of bispecific EV-based cancer immunotherapy, which may inspire treatments against various types of tumors with different surface antigens and even a patient-tailored therapy.
