PMID- 33282892
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201208
IS  - 2296-858X (Print)
IS  - 2296-858X (Electronic)
IS  - 2296-858X (Linking)
VI  - 7
DP  - 2020
TI  - Characterization of Donor Variability for gammadelta T Cell ex vivo Expansion and 
      Development of an Allogeneic gammadelta T Cell Immunotherapy.
PG  - 588453
LID - 10.3389/fmed.2020.588453 [doi]
LID - 588453
AB  - Gamma delta (gammadelta) T cells recently emerged as an attractive candidate for cancer 
      immunotherapy treatments due to their inherent cytotoxicity against both 
      hematological and solid tumors. Moreover, gammadelta T cells provide a platform for the 
      development of allogeneic cell therapies, as they can recognize antigens 
      independent of MHC recognition and without the requirement for a chimeric antigen 
      receptor. However, gammadelta T cell adoptive cell therapy depends on ex vivo expansion 
      to manufacture sufficient cell product numbers, which remains challenging and 
      limited by inter-donor variability. In the current study, we characterize the 
      differences in expansion of gammadelta T cells from various donors that expand (EX) and 
      donors that fail to expand, i.e., non-expanders (NE). Further, we demonstrate 
      that IL-21 can be used to increase the expansion potential of NE. In order to 
      reduce the risk of graft vs. host disease (GVHD) induced by an allogeneic T cell 
      product, alphabeta T cell depletions must be considered due to the potential for HLA 
      mismatch. Typically, alphabeta T cell depletions are performed at the end of expansion, 
      prior to infusion. We show that gammadelta T cell cultures can be successfully alphabeta 
      depleted on day 6 of expansion, providing a better environment for the gammadelta T cells 
      to expand, and that the alphabeta T cell population remains below clinically acceptable 
      standards for T cell-depleted allogeneic stem cell products. Finally, we assess 
      the potential for a mixed donor gammadelta T cell therapy and characterize the effects of 
      cryopreservation on gammadelta T cells. Collectively, these studies support the 
      development of an improved allogeneic gammadelta T cell product and suggest the 
      possibility of using mixed donor gammadelta T cell immunotherapies.
CI  - Copyright (c) 2020 Burnham, Zoine, Story, Garimalla, Gibson, Rae, Williams, Bixby, 
      Archer, Doering and Spencer.
FAU - Burnham, Rebecca E
AU  - Burnham RE
AD  - Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Emory 
      University School of Medicine, Atlanta, GA, United States.
AD  - Molecular and Systems Pharmacology Program, Graduate Division of Biological and 
      Biomedical Sciences, Emory University School of Medicine, Atlanta, GA, United 
      States.
FAU - Zoine, Jaquelyn T
AU  - Zoine JT
AD  - Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Emory 
      University School of Medicine, Atlanta, GA, United States.
AD  - Cancer Biology Program, Graduate Division of Biological and Biomedical Sciences, 
      Emory University School of Medicine, Atlanta, GA, United States.
FAU - Story, Jamie Y
AU  - Story JY
AD  - Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Emory 
      University School of Medicine, Atlanta, GA, United States.
AD  - Molecular and Systems Pharmacology Program, Graduate Division of Biological and 
      Biomedical Sciences, Emory University School of Medicine, Atlanta, GA, United 
      States.
FAU - Garimalla, Swetha N
AU  - Garimalla SN
AD  - School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, 
      United States.
FAU - Gibson, Greg
AU  - Gibson G
AD  - School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, 
      United States.
FAU - Rae, Aaron
AU  - Rae A
AD  - Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Emory 
      University School of Medicine, Atlanta, GA, United States.
FAU - Williams, Erich
AU  - Williams E
AD  - Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Emory 
      University School of Medicine, Atlanta, GA, United States.
FAU - Bixby, Lisa
AU  - Bixby L
AD  - Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Emory 
      University School of Medicine, Atlanta, GA, United States.
FAU - Archer, David
AU  - Archer D
AD  - Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Emory 
      University School of Medicine, Atlanta, GA, United States.
FAU - Doering, Christopher B
AU  - Doering CB
AD  - Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Emory 
      University School of Medicine, Atlanta, GA, United States.
FAU - Spencer, H Trent
AU  - Spencer HT
AD  - Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Emory 
      University School of Medicine, Atlanta, GA, United States.
LA  - eng
PT  - Journal Article
DEP - 20201113
PL  - Switzerland
TA  - Front Med (Lausanne)
JT  - Frontiers in medicine
JID - 101648047
PMC - PMC7691424
OTO - NOTNLM
OT  - allogeneic cell products
OT  - ex vivo expanded T cells
OT  - gamma delta (gammadelta) T cells
OT  - mixed cell product
OT  - serum free expansion
EDAT- 2020/12/08 06:00
MHDA- 2020/12/08 06:01
PMCR- 2020/11/13
CRDT- 2020/12/07 05:35
PHST- 2020/07/28 00:00 [received]
PHST- 2020/10/12 00:00 [accepted]
PHST- 2020/12/07 05:35 [entrez]
PHST- 2020/12/08 06:00 [pubmed]
PHST- 2020/12/08 06:01 [medline]
PHST- 2020/11/13 00:00 [pmc-release]
AID - 10.3389/fmed.2020.588453 [doi]
PST - epublish
SO  - Front Med (Lausanne). 2020 Nov 13;7:588453. doi: 10.3389/fmed.2020.588453. 
      eCollection 2020.