PMID- 38468291
OWN - NLM
STAT- MEDLINE
DCOM- 20240313
LR  - 20240403
IS  - 1476-4598 (Electronic)
IS  - 1476-4598 (Linking)
VI  - 23
IP  - 1
DP  - 2024 Mar 11
TI  - The construction of modular universal chimeric antigen receptor T (MU-CAR-T) 
      cells by covalent linkage of allogeneic T cells and various antibody fragments.
PG  - 53
LID - 10.1186/s12943-024-01938-8 [doi]
LID - 53
AB  - BACKGROUND: Chimeric antigen receptor-T (CAR-T) cells therapy is one of the novel 
      immunotherapeutic approaches with significant clinical success. However, their 
      applications are limited because of long preparation time, high cost, and 
      interpersonal variations. Although the manufacture of universal CAR-T (U-CAR-T) 
      cells have significantly improved, they are still not a stable and unified cell 
      bank. METHODS: Here, we tried to further improve the convenience and flexibility 
      of U-CAR-T cells by constructing novel modular universal CAR-T (MU-CAR-T) cells. 
      For this purpose, we initially screened healthy donors and cultured their T cells 
      to obtain a higher proportion of stem cell-like memory T (T(SCM)) cells, which 
      exhibit robust self-renewal capacity, sustainability and cytotoxicity. To reduce 
      the alloreactivity, the T cells were further edited by double knockout of the T 
      cell receptor (TCR) and class I human leukocyte antigen (HLA-I) genes utilizing 
      the CRISPR/Cas9 system. The well-growing and genetically stable universal cells 
      carrying the CAR-moiety were then stored as a stable and unified cell bank. 
      Subsequently, the SDcatcher/GVoptiTag system, which generate an isopeptide bond, 
      was used to covalently connect the purified scFvs of antibody targeting different 
      antigens to the recovered CAR-T cells. RESULTS: The resulting CAR-T cells can 
      perform different functions by specifically targeting various cells, such as the 
      eradication of human immunodeficiency virus type 1 (HIV-1)-latenly-infected cells 
      or elimination of T lymphoma cells, with similar efficiency as the traditional 
      CAR-T cells did. CONCLUSION: Taken together, our strategy allows the production 
      of CAR-T cells more modularization, and makes the quality control and 
      pharmaceutic manufacture of CAR-T cells more feasible.
CI  - (c) 2024. The Author(s).
FAU - Chen, Tao
AU  - Chen T
AD  - Institute of Human Virology, Department of Pathogen Biology and Biosecurity, Key 
      Laboratory of Tropical Disease Control of Ministry Education, Guangdong 
      Engineering Research Center for Antimicrobial Agent and Immunotechnology, 
      Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
AD  - Guangzhou National Laboratory, Guangzhou International Bio-Island, Guangzhou, 
      510005, China.
FAU - Deng, Jieyi
AU  - Deng J
AD  - Institute of Human Virology, Department of Pathogen Biology and Biosecurity, Key 
      Laboratory of Tropical Disease Control of Ministry Education, Guangdong 
      Engineering Research Center for Antimicrobial Agent and Immunotechnology, 
      Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
FAU - Zhang, Yongli
AU  - Zhang Y
AD  - Institute of Human Virology, Department of Pathogen Biology and Biosecurity, Key 
      Laboratory of Tropical Disease Control of Ministry Education, Guangdong 
      Engineering Research Center for Antimicrobial Agent and Immunotechnology, 
      Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
FAU - Liu, Bingfeng
AU  - Liu B
AD  - Institute of Human Virology, Department of Pathogen Biology and Biosecurity, Key 
      Laboratory of Tropical Disease Control of Ministry Education, Guangdong 
      Engineering Research Center for Antimicrobial Agent and Immunotechnology, 
      Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
FAU - Liu, Ruxin
AU  - Liu R
AD  - Institute of Human Virology, Department of Pathogen Biology and Biosecurity, Key 
      Laboratory of Tropical Disease Control of Ministry Education, Guangdong 
      Engineering Research Center for Antimicrobial Agent and Immunotechnology, 
      Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
FAU - Zhu, Yiqiang
AU  - Zhu Y
AD  - Institute of Human Virology, Department of Pathogen Biology and Biosecurity, Key 
      Laboratory of Tropical Disease Control of Ministry Education, Guangdong 
      Engineering Research Center for Antimicrobial Agent and Immunotechnology, 
      Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
AD  - Guangzhou National Laboratory, Guangzhou International Bio-Island, Guangzhou, 
      510005, China.
FAU - Zhou, Mo
AU  - Zhou M
AD  - Institute of Human Virology, Department of Pathogen Biology and Biosecurity, Key 
      Laboratory of Tropical Disease Control of Ministry Education, Guangdong 
      Engineering Research Center for Antimicrobial Agent and Immunotechnology, 
      Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
FAU - Lin, Yingtong
AU  - Lin Y
AD  - Institute of Human Virology, Department of Pathogen Biology and Biosecurity, Key 
      Laboratory of Tropical Disease Control of Ministry Education, Guangdong 
      Engineering Research Center for Antimicrobial Agent and Immunotechnology, 
      Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
FAU - Xia, Baijin
AU  - Xia B
AD  - Institute of Human Virology, Department of Pathogen Biology and Biosecurity, Key 
      Laboratory of Tropical Disease Control of Ministry Education, Guangdong 
      Engineering Research Center for Antimicrobial Agent and Immunotechnology, 
      Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
FAU - Lin, Keming
AU  - Lin K
AD  - Institute of Human Virology, Department of Pathogen Biology and Biosecurity, Key 
      Laboratory of Tropical Disease Control of Ministry Education, Guangdong 
      Engineering Research Center for Antimicrobial Agent and Immunotechnology, 
      Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
FAU - Ma, Xiancai
AU  - Ma X
AD  - Guangzhou National Laboratory, Guangzhou International Bio-Island, Guangzhou, 
      510005, China. ma_xiancai@gzlab.ac.cn.
AD  - State Key Laboratory of Respiratory Disease, National Clinical Research Center 
      for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First 
      Affiliated Hospital of Guangzhou Medical University, Guangzhou, 511400, China. 
      ma_xiancai@gzlab.ac.cn.
FAU - Zhang, Hui
AU  - Zhang H
AD  - Institute of Human Virology, Department of Pathogen Biology and Biosecurity, Key 
      Laboratory of Tropical Disease Control of Ministry Education, Guangdong 
      Engineering Research Center for Antimicrobial Agent and Immunotechnology, 
      Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China. 
      zhangh92@mail.sysu.edu.cn.
AD  - Guangzhou National Laboratory, Guangzhou International Bio-Island, Guangzhou, 
      510005, China. zhangh92@mail.sysu.edu.cn.
LA  - eng
GR  - 82102385/the National Natural Science Foundation of China (NSFC)/
GR  - 2022YFC0870700/the National Key R&D Program of Department of Science and 
      Technology of China/
GR  - 92169201/the Important Key Program of Natural Science Foundation of China (NSFC)/
GR  - 82150710553/the Exchange Program of NSFC/
GR  - EKPG21-24/the Emergency Key Program of Guangzhou National Laboratory/
GR  - 2022B1111020004/the Key R&D Program of Department of Science and Technology 
      of Guangdong/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20240311
PL  - England
TA  - Mol Cancer
JT  - Molecular cancer
JID - 101147698
RN  - 0 (Receptors, Chimeric Antigen)
RN  - 0 (Immunoglobulin Fragments)
RN  - 0 (Receptors, Antigen, T-Cell)
SB  - IM
MH  - Humans
MH  - *Receptors, Chimeric Antigen/genetics/metabolism
MH  - Immunoglobulin Fragments/metabolism
MH  - T-Lymphocytes
MH  - Receptors, Antigen, T-Cell/metabolism
MH  - Immunotherapy, Adoptive/methods
MH  - *Hematopoietic Stem Cell Transplantation
PMC - PMC10926606
OTO - NOTNLM
OT  - HIV-1
OT  - Modular
OT  - SDcatcher/GVoptiTag
OT  - T cell lymphoma
OT  - Universal CAR-T
COIS- The authors declare no competing interests.
EDAT- 2024/03/12 06:42
MHDA- 2024/03/13 06:47
PMCR- 2024/03/11
CRDT- 2024/03/12 01:18
PHST- 2023/10/27 00:00 [received]
PHST- 2024/01/09 00:00 [accepted]
PHST- 2024/03/13 06:47 [medline]
PHST- 2024/03/12 06:42 [pubmed]
PHST- 2024/03/12 01:18 [entrez]
PHST- 2024/03/11 00:00 [pmc-release]
AID - 10.1186/s12943-024-01938-8 [pii]
AID - 1938 [pii]
AID - 10.1186/s12943-024-01938-8 [doi]
PST - epublish
SO  - Mol Cancer. 2024 Mar 11;23(1):53. doi: 10.1186/s12943-024-01938-8.