PMID- 37995568
OWN - NLM
STAT- MEDLINE
DCOM- 20240104
LR  - 20240207
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 126
DP  - 2024 Jan 5
TI  - Comparative evaluation of antitumor effects of TNF superfamily costimulatory 
      ligands delivered by mesenchymal stem cells.
PG  - 111249
LID - S1567-5769(23)01576-X [pii]
LID - 10.1016/j.intimp.2023.111249 [doi]
AB  - Stimulation of costimulatory receptors serves as an alternative immunotherapeutic 
      strategy other than checkpoint inhibition. However, systemic administration of 
      the agonistic antibodies is associated with severe toxicities, which is one of 
      the major obstacles for their clinical application. This study aimed to develop a 
      mesenchymal stem cell (MSC)-based system for tumor-targeted delivery of TNF 
      superfamily ligands and assess their potential in enhancing antitumor immunity. 
      Here we established an MSC-based system for tumor-targeted delivery of TNF 
      superfamily ligands, including TNFSF4, 9 and 18. The TNFSF receptors (TNFRSFs) 
      were evaluated in mouse models and patient samples for lung and colorectal 
      cancers. TNFRSFs were all expressed at various levels on tumor-infiltrated 
      lymphocytes, with TNFRSF18 being the most prevalent receptor. Human umbilical 
      cord-derived MSCs expressing these costimulatory ligands (MSC-TNFSFs) effectively 
      activated lymphocytes in vitro and elicited antitumor immunity in mice. TNFSF4 
      showed the least antitumor efficacy in both LLC1 and CT26 tumor models. 
      MSC-TNFSF9 showed the most potent tumor-inhibiting effect in the LLC1 tumor 
      model, while MSCs expressing TNFSF18 in combination with CXCL9 most significantly 
      repressed CT26 tumor growth. Overall, TNFSF9 and TNFSF18 exhibited stronger 
      lymphocyte-stimulating and antitumor activities than TNFSF4. Our study provides 
      evidence that antitumor effects of agonism of different costimulatory receptors 
      may vary in different tumor types and presents a promising approach for targeted 
      delivery of TNF superfamily costimulatory ligands to avoid the systemic 
      toxicities and side effects associated with immune agonist antibodies.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Gui, Liming
AU  - Gui L
AD  - Renji-Med-X Clinical Stem Cell Research Center, Renji Hospital, School of 
      Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, 
      Shanghai, China; Med-X Research Institute, Shanghai Jiao Tong University, 
      Shanghai, China.
FAU - Wang, Zhixue
AU  - Wang Z
AD  - Renji-Med-X Clinical Stem Cell Research Center, Renji Hospital, School of 
      Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, 
      Shanghai, China; Med-X Research Institute, Shanghai Jiao Tong University, 
      Shanghai, China.
FAU - Lou, Weihua
AU  - Lou W
AD  - Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai, China.
FAU - Yekehfallah, Vahid
AU  - Yekehfallah V
AD  - Renji-Med-X Clinical Stem Cell Research Center, Renji Hospital, School of 
      Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, 
      Shanghai, China; Med-X Research Institute, Shanghai Jiao Tong University, 
      Shanghai, China; Current address: Vancouver Prostate Centre, Department of 
      Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
FAU - Basiri, Mohsen
AU  - Basiri M
AD  - Department of Stem Cells and Developmental Biology, Cell Science Research Center, 
      Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
FAU - Gao, Wei-Qiang
AU  - Gao WQ
AD  - Renji-Med-X Clinical Stem Cell Research Center, Renji Hospital, School of 
      Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, 
      Shanghai, China; Med-X Research Institute, Shanghai Jiao Tong University, 
      Shanghai, China.
FAU - Wang, You
AU  - Wang Y
AD  - Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai, China. Electronic address: 
      wangyou6433@renji.com.
FAU - Ma, Bin
AU  - Ma B
AD  - Renji-Med-X Clinical Stem Cell Research Center, Renji Hospital, School of 
      Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, 
      Shanghai, China; Med-X Research Institute, Shanghai Jiao Tong University, 
      Shanghai, China. Electronic address: binma@sjtu.edu.cn.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20231122
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Antibodies)
RN  - 0 (Ligands)
RN  - 0 (OX40 Ligand)
RN  - 0 (TNFSF4 protein, human)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Mice
MH  - *Antibodies/metabolism
MH  - Cell Line, Tumor
MH  - Ligands
MH  - *Mesenchymal Stem Cells/metabolism
MH  - OX40 Ligand/metabolism
OTO - NOTNLM
OT  - Costimulatory ligands
OT  - Costimulatory receptors
OT  - Mesenchymal stem cells
OT  - Tumor necrosis factor superfamily
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/11/24 00:42
MHDA- 2023/12/28 06:42
CRDT- 2023/11/23 18:12
PHST- 2023/08/16 00:00 [received]
PHST- 2023/10/28 00:00 [revised]
PHST- 2023/11/14 00:00 [accepted]
PHST- 2023/12/28 06:42 [medline]
PHST- 2023/11/24 00:42 [pubmed]
PHST- 2023/11/23 18:12 [entrez]
AID - S1567-5769(23)01576-X [pii]
AID - 10.1016/j.intimp.2023.111249 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2024 Jan 5;126:111249. doi: 10.1016/j.intimp.2023.111249. 
      Epub 2023 Nov 22.