PMID- 37738123
OWN - NLM
STAT- MEDLINE
DCOM- 20231106
LR  - 20231109
IS  - 2211-1247 (Electronic)
VI  - 42
IP  - 10
DP  - 2023 Oct 31
TI  - Engineering of dendritic cell bispecific extracellular vesicles for 
      tumor-targeting immunotherapy.
PG  - 113138
LID - S2211-1247(23)01150-6 [pii]
LID - 10.1016/j.celrep.2023.113138 [doi]
AB  - 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.
CI  - Copyright (c) 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Xu, Fang
AU  - Xu F
AD  - 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.
FAU - Jiang, Dongpeng
AU  - Jiang D
AD  - 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.
FAU - Xu, Jialu
AU  - Xu J
AD  - 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.
FAU - Dai, Huaxing
AU  - Dai H
AD  - 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.
FAU - Fan, Qin
AU  - Fan Q
AD  - Institute of Advanced Materials (IAM) and School of Materials Science and 
      Engineering, Nanjing University of Posts & Telecommunications, Nanjing 210000, 
      China.
FAU - Fei, Ziying
AU  - Fei Z
AD  - 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.
FAU - Wang, Beilei
AU  - Wang B
AD  - 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.
FAU - Zhang, Yue
AU  - Zhang Y
AD  - 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.
FAU - Ma, Qingle
AU  - Ma Q
AD  - 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.
FAU - Yang, Qianyu
AU  - Yang Q
AD  - 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.
FAU - Chen, Yitong
AU  - Chen Y
AD  - 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.
FAU - Ogunnaike, Edikan A
AU  - Ogunnaike EA
AD  - Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, 
      University of North Carolina, Chapel Hill, NC 27599, USA.
FAU - Chu, Jianhong
AU  - Chu J
AD  - 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.
FAU - Wang, Chao
AU  - Wang C
AD  - 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.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230921
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (Antigens, Neoplasm)
SB  - IM
MH  - Humans
MH  - *Extracellular Vesicles/metabolism
MH  - *Neoplasms/therapy/metabolism
MH  - Antigens, Neoplasm/metabolism
MH  - Immunotherapy
MH  - Dendritic Cells
OTO - NOTNLM
OT  - CP: Cancer
OT  - CP: Immunology
OT  - bispecific EVs
OT  - cancer immunotherapy
OT  - dendritic cell
OT  - extracellular vesicle
OT  - solid tumor
OT  - targeting
COIS- Declaration of interests The authors declare no competing interests.
EDAT- 2023/09/22 18:42
MHDA- 2023/11/06 06:42
CRDT- 2023/09/22 12:36
PHST- 2022/05/23 00:00 [received]
PHST- 2023/06/10 00:00 [revised]
PHST- 2023/08/30 00:00 [accepted]
PHST- 2023/11/06 06:42 [medline]
PHST- 2023/09/22 18:42 [pubmed]
PHST- 2023/09/22 12:36 [entrez]
AID - S2211-1247(23)01150-6 [pii]
AID - 10.1016/j.celrep.2023.113138 [doi]
PST - ppublish
SO  - Cell Rep. 2023 Oct 31;42(10):113138. doi: 10.1016/j.celrep.2023.113138. Epub 2023 
      Sep 21.