PMID- 30122653
OWN - NLM
STAT- MEDLINE
DCOM- 20191008
LR  - 20191008
IS  - 1477-2566 (Electronic)
IS  - 1465-3249 (Linking)
VI  - 20
IP  - 9
DP  - 2018 Sep
TI  - Generation of multivirus-specific T cells by a single stimulation of peripheral 
      blood mononuclear cells with a peptide mixture using serum-free medium.
PG  - 1182-1190
LID - S1465-3249(18)30520-6 [pii]
LID - 10.1016/j.jcyt.2018.05.009 [doi]
AB  - BACKGROUND: Restoration of virus-specific immunity by virus specific T cells 
      (VSTs) offers an attractive alternative to conventional drugs, and can be highly 
      effective in immunocompromised patients, including hematopoietic stem cell 
      transplant (HSCT) recipients. However, conventional VSTs manufacture requires 
      preparation of specialized antigen-presenting cells (APCs), prolonged ex vivo 
      culture in serum-containing medium and antigen re-stimulation with viruses or 
      viral vectors to provide viral antigens for presentation on APCs. METHODS: To 
      simplify this complex process, we developed a method to generate multiple VSTs by 
      direct stimulation of peripheral blood mononuclear cells (PBMCs) with overlapping 
      peptide libraries in serum-free medium. RESULTS: We generated VSTs that targeted 
      seven viruses (cytomegalovirus [CMV], Epstein-Barr virus [EBV], adenovirus [AdV], 
      human herpesvirus 6 [HHV-6], BK virus [BKV], JC virus [JCV] and Varicella Zoster 
      virus [VZV]) in a single line. The phenotype, growth and specificity of multiple 
      VSTs produced in serum-free medium were equivalent to those generated in 
      conventional serum-containing medium. DISCUSSION: The use of serum-free medium 
      allows this approach to be readily introduced to clinical practice with lower 
      cost, greater reproducibility due to the absence of batch-to-batch variability in 
      serum and without concerns for infectious agents in the serum used. This 
      simplified approach will now be tested in recipients of Human Leukocyte Antigen 
      (HLA)-matched sibling HSCT.
CI  - Copyright (c) 2018. Published by Elsevier Inc.
FAU - Nishiyama-Fujita, Yuriko
AU  - Nishiyama-Fujita Y
AD  - Division of Molecular Therapy, Advanced Clinical Research Center, The Institute 
      of Medical Science, University of Tokyo, Tokyo, Japan.
FAU - Kawana-Tachikawa, A I
AU  - Kawana-Tachikawa AI
AD  - AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
FAU - Ono, Toshiaki
AU  - Ono T
AD  - Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental 
      University Graduate School of Medical and Dental Sciences, Tokyo, Japan.
FAU - Tanaka, Yukie
AU  - Tanaka Y
AD  - Division of Molecular Therapy, Advanced Clinical Research Center, The Institute 
      of Medical Science, University of Tokyo, Tokyo, Japan.
FAU - Kato, Takafumi
AU  - Kato T
AD  - Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental 
      University Graduate School of Medical and Dental Sciences, Tokyo, Japan.
FAU - Heslop, Helen E
AU  - Heslop HE
AD  - Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist 
      Hospital and Texas Children's Hospital, Houston, TX, United States.
FAU - Morio, Tomohiro
AU  - Morio T
AD  - Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental 
      University Graduate School of Medical and Dental Sciences, Tokyo, Japan.
FAU - Takahashi, Satoshi
AU  - Takahashi S
AD  - Division of Molecular Therapy, Advanced Clinical Research Center, The Institute 
      of Medical Science, University of Tokyo, Tokyo, Japan. Electronic address: 
      radius@ims.u-tokyo.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180817
PL  - England
TA  - Cytotherapy
JT  - Cytotherapy
JID - 100895309
RN  - 0 (Antigens, Viral)
RN  - 0 (Culture Media, Serum-Free)
RN  - 0 (Peptide Library)
RN  - 0 (Peptides)
SB  - IM
MH  - Adenoviridae/immunology
MH  - Antigen-Presenting Cells/immunology
MH  - Antigens, Viral/*immunology
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Culture Media, Serum-Free/pharmacology
MH  - Cytomegalovirus/immunology
MH  - Herpesvirus 3, Human/immunology
MH  - Herpesvirus 4, Human/immunology
MH  - Humans
MH  - Immunophenotyping
MH  - Leukocytes, Mononuclear/drug effects/*immunology
MH  - Peptide Library
MH  - Peptides/immunology/*pharmacology
MH  - Reproducibility of Results
MH  - T-Lymphocytes/*immunology/*virology
OTO - NOTNLM
OT  - T lymphocytes
OT  - hematopoietic stem cell transplantation
OT  - serum-free culture medium
OT  - viral antigens
OT  - viral diseases
EDAT- 2018/08/21 06:00
MHDA- 2019/10/09 06:00
CRDT- 2018/08/21 06:00
PHST- 2017/12/02 00:00 [received]
PHST- 2018/05/08 00:00 [revised]
PHST- 2018/05/15 00:00 [accepted]
PHST- 2018/08/21 06:00 [pubmed]
PHST- 2019/10/09 06:00 [medline]
PHST- 2018/08/21 06:00 [entrez]
AID - S1465-3249(18)30520-6 [pii]
AID - 10.1016/j.jcyt.2018.05.009 [doi]
PST - ppublish
SO  - Cytotherapy. 2018 Sep;20(9):1182-1190. doi: 10.1016/j.jcyt.2018.05.009. Epub 2018 
      Aug 17.