PMID- 24176543
OWN - NLM
STAT- MEDLINE
DCOM- 20140818
LR  - 20211021
IS  - 1477-2566 (Electronic)
IS  - 1465-3249 (Print)
IS  - 1465-3249 (Linking)
VI  - 16
IP  - 1
DP  - 2014 Jan
TI  - Genetically engineered fixed K562 cells: potent "off-the-shelf" 
      antigen-presenting cells for generating virus-specific T cells.
PG  - 135-46
LID - S1465-3249(13)00678-6 [pii]
LID - 10.1016/j.jcyt.2013.08.008 [doi]
AB  - BACKGROUND AIMS: The human leukemia cell line K562 represents an attractive 
      platform for creating artificial antigen-presenting cells (aAPC). It is readily 
      expandable, does not express human leukocyte antigen (HLA) class I and II and can 
      be stably transduced with various genes. METHODS: In order to generate 
      cytomegalovirus (CMV) antigen-specific T cells for adoptive immunotherapy, we 
      transduced K562 with HLA-A *0201 in combination with co-stimulatory molecules. 
      RESULTS: In preliminary experiments, irradiated K562 expressing HLA-A *0201 and 
      4-1BBL pulsed with CMV pp65 and IE-1 peptide libraries failed to elicit 
      antigen-specific CD8(+) T cells in HLA-A *0201(+) peripheral blood mononuclear cells 
      (PBMC) or isolated T cells. Both wild-type K562 and aAPC strongly inhibited T 
      cell proliferation to the bacterial superantigen staphylococcal enterotoxin B 
      (SEB) and OKT3 and in mixed lymphocyte reaction (MLR). Transwell experiments 
      suggested that suppression was mediated by a soluble factor; however, MLR 
      inhibition was not reversed using transforming growth factor-beta blocking antibody 
      or prostaglandin E2 inhibitors. Full abrogation of the suppressive activity of 
      K562 on MLR, SEB and OKT3 stimulation was only achieved by brief fixation with 
      0.1% formaldehyde. Fixed, pp65 and IE-1 peptide-loaded aAPC induced robust 
      expansion of CMV-specific T cells. CONCLUSIONS: Fixed gene-modified K562 can 
      serve as effective aAPC to expand CMV-specific cytotoxic T lymphocytes for 
      therapeutic use in patients after stem cell transplantation. Our findings have 
      implications for broader understanding of the immune evasion mechanisms used by 
      leukemia and other tumors.
CI  - Published by Elsevier Inc.
FAU - Tanimoto, Kazushi
AU  - Tanimoto K
AD  - Stem Cell Allogeneic Transplantation Section, Hematology Branch, National Heart, 
      Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA. 
      Electronic address: kazshi.tanimoto@gmail.com.
FAU - Muranski, Pawel
AU  - Muranski P
AD  - Stem Cell Allogeneic Transplantation Section, Hematology Branch, National Heart, 
      Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
FAU - Miner, Samantha
AU  - Miner S
AD  - Stem Cell Allogeneic Transplantation Section, Hematology Branch, National Heart, 
      Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
FAU - Fujiwara, Hiroshi
AU  - Fujiwara H
AD  - Department of Bioregulatory Medicine, Ehime University Graduate School of 
      Medicine, Ehime, Japan.
FAU - Kajigaya, Sachiko
AU  - Kajigaya S
AD  - Stem Cell Allogeneic Transplantation Section, Hematology Branch, National Heart, 
      Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
FAU - Keyvanfar, Keyvan
AU  - Keyvanfar K
AD  - Stem Cell Allogeneic Transplantation Section, Hematology Branch, National Heart, 
      Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
FAU - Hensel, Nancy
AU  - Hensel N
AD  - Stem Cell Allogeneic Transplantation Section, Hematology Branch, National Heart, 
      Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
FAU - Barrett, A John
AU  - Barrett AJ
AD  - Stem Cell Allogeneic Transplantation Section, Hematology Branch, National Heart, 
      Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
FAU - Melenhorst, J Joseph
AU  - Melenhorst JJ
AD  - Stem Cell Allogeneic Transplantation Section, Hematology Branch, National Heart, 
      Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA; 
      Abramson Cancer Center, Department of Pathology and Laboratory Medicine, Perelman 
      School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
LA  - eng
GR  - Z01 HL002342-09/Intramural NIH HHS/United States
GR  - Z01 HL002342-13/Intramural NIH HHS/United States
GR  - Z01 HL002342-14/Intramural NIH HHS/United States
PT  - Journal Article
DEP - 20131029
PL  - England
TA  - Cytotherapy
JT  - Cytotherapy
JID - 100895309
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Antigen-Presenting Cells/*immunology
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Cytomegalovirus Infections/*immunology/therapy
MH  - *Genetic Engineering
MH  - HLA Antigens/immunology
MH  - Humans
MH  - K562 Cells
MH  - Leukocytes, Mononuclear/*immunology
MH  - Lymphocyte Activation/immunology
MH  - T-Lymphocytes, Cytotoxic/immunology
PMC - PMC6755681
MID - NIHMS537238
OTO - NOTNLM
OT  - artificial APC
OT  - cytomegalovirus
OT  - cytotoxic T cell
OT  - fixation
COIS- Disclosure of Interest The authors declare no potential conflicts of interest in 
      this study.
EDAT- 2013/11/02 06:00
MHDA- 2014/08/19 06:00
PMCR- 2019/09/23
CRDT- 2013/11/02 06:00
PHST- 2013/02/21 00:00 [received]
PHST- 2013/08/13 00:00 [revised]
PHST- 2013/08/21 00:00 [accepted]
PHST- 2013/11/02 06:00 [entrez]
PHST- 2013/11/02 06:00 [pubmed]
PHST- 2014/08/19 06:00 [medline]
PHST- 2019/09/23 00:00 [pmc-release]
AID - S1465-3249(13)00678-6 [pii]
AID - 10.1016/j.jcyt.2013.08.008 [doi]
PST - ppublish
SO  - Cytotherapy. 2014 Jan;16(1):135-46. doi: 10.1016/j.jcyt.2013.08.008. Epub 2013 
      Oct 29.