PMID- 34323289
OWN - NLM
STAT- MEDLINE
DCOM- 20211220
LR  - 20231213
IS  - 1521-4141 (Electronic)
IS  - 0014-2980 (Print)
IS  - 0014-2980 (Linking)
VI  - 51
IP  - 10
DP  - 2021 Oct
TI  - Mutant B2M-HLA-E and B2M-HLA-G fusion proteins protects universal chimeric 
      antigen receptor-modified T cells from allogeneic NK cell-mediated lysis.
PG  - 2513-2521
LID - 10.1002/eji.202049107 [doi]
AB  - Recent studies have indicated the antitumor activity and reduced allogeneic 
      response of universal chimeric antigen receptor-modified T (UCAR T) cells lacking 
      endogenous T cell receptors and beta-2 microglobulin (B2M) generated using 
      gene-editing technologies. However, these cells are vulnerable to lysis by 
      allogeneic natural killer (NK) cells due to their lack of human leukocyte antigen 
      (HLA) class I molecule expression. Here, constitutive expression of mutant 
      B2M-HLA-E (mBE) and B2M-HLA-G (mBG) fusion proteins in anti-CD19 UCAR T (UCAR 
      T-19) cells was conducted to protect against allogeneic NK cell-mediated lysis. 
      The ability of cells expressing mBE or mBG to resist NK cell-mediated lysis was 
      observed in gene-edited Jurkat CAR19 cells. UCAR T-19 cells constitutively 
      expressing the mBE and mBG fusion proteins were manufactured and showed effective 
      and specific anti-tumor activity. Constitutive expression of the mBE and mBG 
      fusion proteins in UCAR T-19 cells prevented allogeneic NK cell-mediated lysis. 
      In addition, these cells were not recognizable by allogeneic T cells. Additional 
      experiments, including those in animal models and clinical trials, are required 
      to evaluate the safety and efficacy of UCAR T-19 cells that constitutively 
      express mBE and mBG.
CI  - (c) 2021 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.
FAU - Guo, Yelei
AU  - Guo Y
AD  - Department of Bio-therapeutic, the First Medical Centre, Chinese PLA General 
      Hospital, Beijing, China.
FAU - Xu, Beilei
AU  - Xu B
AD  - State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, 
      Chinese Academy of Sciences, Beijing, China.
FAU - Wu, Zhiqiang
AU  - Wu Z
AD  - Department of Bio-therapeutic, the First Medical Centre, Chinese PLA General 
      Hospital, Beijing, China.
FAU - Bo, Jian
AU  - Bo J
AD  - Department of Hematology, the First Medical Centre, Chinese PLA General Hospital, 
      Beijing, China.
FAU - Tong, Chuan
AU  - Tong C
AD  - Department of Bio-therapeutic, the First Medical Centre, Chinese PLA General 
      Hospital, Beijing, China.
FAU - Chen, Deyun
AU  - Chen D
AD  - Department of Bio-therapeutic, the First Medical Centre, Chinese PLA General 
      Hospital, Beijing, China.
FAU - Wang, Jin
AU  - Wang J
AD  - Department of Outpatient, the Sixth Medical Centre, Chinese PLA General Hospital, 
      Beijing, China.
FAU - Wang, Haoyi
AU  - Wang H
AD  - State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, 
      Chinese Academy of Sciences, Beijing, China.
FAU - Wang, Yao
AU  - Wang Y
AD  - Department of Bio-therapeutic, the First Medical Centre, Chinese PLA General 
      Hospital, Beijing, China.
FAU - Han, Weidong
AU  - Han W
AD  - Department of Bio-therapeutic, the First Medical Centre, Chinese PLA General 
      Hospital, Beijing, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210819
PL  - Germany
TA  - Eur J Immunol
JT  - European journal of immunology
JID - 1273201
RN  - 0 (Antigens, CD19)
RN  - 0 (B2M protein, human)
RN  - 0 (HLA-G Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Receptors, Chimeric Antigen)
RN  - 0 (beta 2-Microglobulin)
SB  - IM
MH  - Antigens, CD19/immunology
MH  - Cytotoxicity, Immunologic/*genetics
MH  - Gene Knockout Techniques
MH  - HLA-G Antigens/*genetics/immunology
MH  - Histocompatibility Antigens Class I/*genetics/immunology
MH  - Humans
MH  - Immunophenotyping
MH  - Killer Cells, Natural/immunology/metabolism
MH  - Lymphocyte Activation/immunology
MH  - *Mutation
MH  - Receptors, Antigen, T-Cell/genetics/immunology
MH  - Receptors, Chimeric Antigen/*genetics/immunology
MH  - T-Lymphocytes/*immunology/*metabolism
MH  - beta 2-Microglobulin/*genetics/immunology
MH  - HLA-E Antigens
PMC - PMC9292285
OTO - NOTNLM
OT  - HLA-E
OT  - HLA-G
OT  - NK cells
OT  - chimeric antigen receptor
OT  - universal CAR T
COIS- The authors declare no commercial or financial conflict of interest.
EDAT- 2021/07/30 06:00
MHDA- 2021/12/21 06:00
PMCR- 2022/07/18
CRDT- 2021/07/29 08:47
PHST- 2021/03/20 00:00 [revised]
PHST- 2020/12/07 00:00 [received]
PHST- 2021/07/30 06:00 [pubmed]
PHST- 2021/12/21 06:00 [medline]
PHST- 2021/07/29 08:47 [entrez]
PHST- 2022/07/18 00:00 [pmc-release]
AID - EJI5146 [pii]
AID - 10.1002/eji.202049107 [doi]
PST - ppublish
SO  - Eur J Immunol. 2021 Oct;51(10):2513-2521. doi: 10.1002/eji.202049107. Epub 2021 
      Aug 19.