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

doi:10.1016/j.celrep.2023.113138

Engineering of dendritic cell bispecific extracellular vesicles for tumor-targeting immunotherapy

Cell Rep. 2023 Oct 31;42(10):113138. doi: 10.1016/j.celrep.2023.113138. Epub 2023 Sep 21.

Authors

Fang Xu¹, Dongpeng Jiang², Jialu Xu¹, Huaxing Dai¹, Qin Fan³, Ziying Fei¹, Beilei Wang¹, Yue Zhang¹, Qingle Ma¹, Qianyu Yang¹, Yitong Chen¹, Edikan A Ogunnaike⁴, Jianhong Chu⁵, Chao Wang⁶

Affiliations

¹ 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.
² 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.
³ Institute of Advanced Materials (IAM) and School of Materials Science and Engineering, Nanjing University of Posts & Telecommunications, Nanjing 210000, China.
⁴ Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.
⁵ 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. Electronic address: chujianhong@hotmail.com.
⁶ 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. Electronic address: cwang@suda.edu.cn.

PMID: 37738123
DOI: 10.1016/j.celrep.2023.113138

Abstract

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.

Keywords: CP: Cancer; CP: Immunology; bispecific EVs; cancer immunotherapy; dendritic cell; extracellular vesicle; solid tumor; targeting.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antigens, Neoplasm / metabolism
Dendritic Cells
Extracellular Vesicles* / metabolism
Humans
Immunotherapy
Neoplasms* / metabolism
Neoplasms* / therapy

Substances

Antigens, Neoplasm