PMID- 29724686
OWN - NLM
STAT- MEDLINE
DCOM- 20190611
LR  - 20210109
IS  - 1525-0024 (Electronic)
IS  - 1525-0016 (Print)
IS  - 1525-0016 (Linking)
VI  - 26
IP  - 6
DP  - 2018 Jun 6
TI  - HIV-Specific T Cells Generated from Naive T Cells Suppress HIV In Vitro and 
      Recognize Wide Epitope Breadths.
PG  - 1435-1446
LID - S1525-0016(18)30166-7 [pii]
LID - 10.1016/j.ymthe.2018.04.009 [doi]
AB  - The Berlin Patient represents the first and only functional HIV cure achieved by 
      hematopoietic stem cell transplant (HSCT). In subsequent efforts to replicate 
      this result, HIV rebounded post-HSCT after withdrawal of antiretroviral therapy. 
      Providing HIV-specific immunity through adoptive T cell therapy may prevent HIV 
      rebound post-HSCT by eliminating newly infected cells before they can seed 
      systemic infection. Adoptive T cell therapy has demonstrated success in boosting 
      Epstein-Barr virus and cytomegalovirus-specific immunity post-HSCT, controlling 
      viral reactivation. However, T cell immunotherapies to boost HIV-specific 
      immunity have been limited by single-epitope specificity and minimal persistence 
      or efficacy in vivo. To improve this strategy, we sought to generate allogeneic 
      HIV-specific T cells from human leukocyte antigen (HLA)-A02+ HIV-negative adult 
      or cord blood donors. We focused on HLA-A02+ donors due to well-characterized 
      epitope restrictions observed in HIV+ populations. We show that multi-antigen 
      HIV-specific T cells can be generated from naive T cells of both cord blood and 
      adults using a reproducible good manufacturing practice (GMP)-grade protocol. 
      This product lysed antigen-pulsed targets and suppressed active HIV in vitro. 
      Interestingly, these cells displayed broad epitope recognition despite lacking 
      recognition of the common HLA-A02-restricted HIV epitope Gag SL9. This first 
      demonstration of functional multi-antigen HIV-specific T cells has implications 
      for improving treatment of HIV through allogeneic HSCT.
CI  - Copyright (c) 2018. Published by Elsevier Inc.
FAU - Patel, Shabnum
AU  - Patel S
AD  - Center for Cancer and Immunology Research, Children's National Health System, 
      Washington, DC 20010, USA; Cancer Center, Department of Pediatrics, The George 
      Washington University, Washington, DC 20037, USA.
FAU - Chorvinsky, Elizabeth
AU  - Chorvinsky E
AD  - Center for Cancer and Immunology Research, Children's National Health System, 
      Washington, DC 20010, USA.
FAU - Albihani, Shuroug
AU  - Albihani S
AD  - Center for Cancer and Immunology Research, Children's National Health System, 
      Washington, DC 20010, USA.
FAU - Cruz, Conrad Russell
AU  - Cruz CR
AD  - Center for Cancer and Immunology Research, Children's National Health System, 
      Washington, DC 20010, USA; Cancer Center, Department of Pediatrics, The George 
      Washington University, Washington, DC 20037, USA.
FAU - Jones, R Brad
AU  - Jones RB
AD  - Department of Microbiology, Immunology, and Tropical Medicine, The George 
      Washington University, Washington, DC 20037, USA.
FAU - Shpall, Elizabeth J
AU  - Shpall EJ
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
FAU - Margolis, David M
AU  - Margolis DM
AD  - University of North Carolina HIV Cure Center, University of North Carolina at 
      Chapel Hill, Chapel Hill, NC 27599, USA.
FAU - Ambinder, Richard F
AU  - Ambinder RF
AD  - Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of 
      Medicine, Baltimore, MD 21231, USA.
FAU - Bollard, Catherine M
AU  - Bollard CM
AD  - Center for Cancer and Immunology Research, Children's National Health System, 
      Washington, DC 20010, USA; Cancer Center, Department of Pediatrics, The George 
      Washington University, Washington, DC 20037, USA. Electronic address: 
      cbollard@cnmc.org.
LA  - eng
GR  - P01 CA148600/CA/NCI NIH HHS/United States
GR  - R01 HL132791/HL/NHLBI NIH HHS/United States
GR  - UM1 AI126617/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20180412
PL  - United States
TA  - Mol Ther
JT  - Molecular therapy : the journal of the American Society of Gene Therapy
JID - 100890581
RN  - 0 (Epitopes)
SB  - IM
MH  - Allografts
MH  - CD4-Positive T-Lymphocytes/immunology/metabolism
MH  - Cells, Cultured
MH  - Cytomegalovirus/immunology
MH  - Epitope Mapping
MH  - Epitopes/immunology
MH  - Flow Cytometry
MH  - HIV-1/*immunology
MH  - Humans
MH  - Immunotherapy, Adoptive
MH  - T-Lymphocytes/*immunology/metabolism
PMC - PMC5986979
OTO - NOTNLM
OT  - HIV-specific T cells
OT  - adoptive T cell therapy
OT  - allogeneic transplant
EDAT- 2018/05/05 06:00
MHDA- 2019/06/14 06:00
PMCR- 2019/06/06
CRDT- 2018/05/05 06:00
PHST- 2018/01/31 00:00 [received]
PHST- 2018/04/02 00:00 [revised]
PHST- 2018/04/05 00:00 [accepted]
PHST- 2018/05/05 06:00 [pubmed]
PHST- 2019/06/14 06:00 [medline]
PHST- 2018/05/05 06:00 [entrez]
PHST- 2019/06/06 00:00 [pmc-release]
AID - S1525-0016(18)30166-7 [pii]
AID - 10.1016/j.ymthe.2018.04.009 [doi]
PST - ppublish
SO  - Mol Ther. 2018 Jun 6;26(6):1435-1446. doi: 10.1016/j.ymthe.2018.04.009. Epub 2018 
      Apr 12.