PMID- 30396848
OWN - NLM
STAT- MEDLINE
DCOM- 20200224
LR  - 20200309
IS  - 1477-2566 (Electronic)
IS  - 1465-3249 (Print)
IS  - 1465-3249 (Linking)
VI  - 21
IP  - 2
DP  - 2019 Feb
TI  - Epstein-Barr Virus (EBV)-derived BARF1 encodes CD4- and CD8-restricted epitopes 
      as targets for T-cell immunotherapy.
PG  - 212-223
LID - S1465-3249(18)30562-0 [pii]
LID - 10.1016/j.jcyt.2018.08.001 [doi]
AB  - BACKGROUND AIMS: EBV type II latency tumors, such as Hodgkin lymphoma (HL), 
      Non-Hodgkin lymphoma (NHL) and nasopharyngeal carcinoma, express a limited array 
      of EBV antigens including Epstein-Barr nuclear antigen (EBNA)1, latent membrane 
      protein (LMP)1, LMP2, and BamH1-A right frame 1 (BARF1). Adoptive immunotherapy 
      for these malignancies have focused on EBNA1, LMP1 and LMP2 because little is 
      known about the cellular immune response to BARF1. METHODS: To investigate 
      whether BARF1 is a potential T-cell immunotherapy target, we determined the 
      frequency of BARF1-specific T-cell responses in the peripheral blood of 
      EBV-seropositive healthy donor and patients with EBV-positive malignancies, 
      mapped epitopes and evaluated the effector function of ex vivo-generated 
      BARF1-specific T-cell lines. RESULTS: BARF1-specific T cells were present in the 
      peripheral blood of 12/16 (75%) EBV-positive healthy donors and 13/20 (65%) 
      patients with EBV-positive malignancies. Ex vivo expanded BARF1-specific T-cell 
      lines contained CD4- and CD8-positive T-cell subpopulations, and we identified 23 
      BARF1 peptides, which encoded major histocompatibility complex class I- and/or 
      II-restricted epitopes. Epitope mapping identified one human leukocyte antigen 
      (HLA)-A*02-restricted epitope that was recognized by 50% of HLA-A*02, 
      EBV-seropositive donors and one HLA-B*15(62)-restricted epitope. Exvivo expanded 
      BARF1-specific T cells recognized and killed autologous, EBV-transformed 
      lymphoblastoid cell lines and partially HLA-matched EBV-positive lymphoma cell 
      lines. DISCUSSION: BARF1 should be considered as an immunotherapy target for EBV 
      type II (and III) latency. Targeting BARF1, in addition to EBNA1, LMP1 and LMP2, 
      has the potential to improve the efficacy of current T-cell immunotherapy 
      approaches for these malignancies.
CI  - Copyright (c) 2018 International Society for Cell and Gene Therapy. Published by 
      Elsevier Inc. All rights reserved.
FAU - Kalra, Mamta
AU  - Kalra M
AD  - Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist, 
      Baylor College of Medicine, Houston, Texas, USA; Texas Children's Cancer Center, 
      Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA; 
      Departments of Pediatrics.
FAU - Gerdemann, Ulrike
AU  - Gerdemann U
AD  - Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist, 
      Baylor College of Medicine, Houston, Texas, USA; Texas Children's Cancer Center, 
      Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA; 
      Departments of Pediatrics.
FAU - Luu, Jessica D
AU  - Luu JD
AD  - Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist, 
      Baylor College of Medicine, Houston, Texas, USA; Texas Children's Cancer Center, 
      Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA; 
      Departments of Pediatrics.
FAU - Ngo, Minthran C
AU  - Ngo MC
AD  - Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist, 
      Baylor College of Medicine, Houston, Texas, USA; Texas Children's Cancer Center, 
      Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA; 
      Departments of Pediatrics.
FAU - Leen, Ann M
AU  - Leen AM
AD  - Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist, 
      Baylor College of Medicine, Houston, Texas, USA; Texas Children's Cancer Center, 
      Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA; 
      Departments of Pediatrics; Pathology and Immunology.
FAU - Louis, Chrystal U
AU  - Louis CU
AD  - Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist, 
      Baylor College of Medicine, Houston, Texas, USA; Texas Children's Cancer Center, 
      Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA; 
      Departments of Pediatrics.
FAU - Rooney, Cliona M
AU  - Rooney CM
AD  - Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist, 
      Baylor College of Medicine, Houston, Texas, USA; Texas Children's Cancer Center, 
      Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA; 
      Departments of Pediatrics; Pathology and Immunology; Molecular Virology and 
      Microbiology, Baylor College of Medicine, Houston, Texas, USA.
FAU - Gottschalk, Stephen
AU  - Gottschalk S
AD  - Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist, 
      Baylor College of Medicine, Houston, Texas, USA; Texas Children's Cancer Center, 
      Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA; 
      Departments of Pediatrics; Pathology and Immunology. Electronic address: 
      stephen.gottschalk@stjude.org.
LA  - eng
GR  - P01 CA094237/CA/NCI NIH HHS/United States
GR  - P30 CA125123/CA/NCI NIH HHS/United States
GR  - P50 CA126752/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20181102
PL  - England
TA  - Cytotherapy
JT  - Cytotherapy
JID - 100895309
RN  - 0 (BARF1 protein, Human herpesvirus 4)
RN  - 0 (BZLF1 protein, Herpesvirus 4, Human)
RN  - 0 (Epitopes)
RN  - 0 (Epstein-Barr Virus Nuclear Antigens)
RN  - 0 (Trans-Activators)
RN  - 0 (Viral Matrix Proteins)
RN  - 0 (Viral Proteins)
RN  - O5GA75RST7 (EBV-encoded nuclear antigen 1)
SB  - IM
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Cell Line, Tumor
MH  - Epitopes/*immunology
MH  - Epstein-Barr Virus Nuclear Antigens/immunology
MH  - HEK293 Cells
MH  - Herpesvirus 4, Human/*immunology
MH  - Humans
MH  - Immunotherapy/*methods
MH  - Immunotherapy, Adoptive/*methods
MH  - Lymphoma/*therapy/virology
MH  - Trans-Activators/immunology
MH  - Viral Matrix Proteins/immunology
MH  - Viral Proteins/*immunology
PMC - PMC6435433
MID - NIHMS1503330
OTO - NOTNLM
OT  - BARF1
OT  - EBV
OT  - EBV-positive malignancies
OT  - immunotherapy
COIS- DISCLOSURE OF INTEREST AML and CMR are cofounders of ViraCyte. UG, MCN, AML, CUL, 
      CMR, SG have patent applications in the field of T-cell and gene-modified T-cell 
      therapy for cancer.
EDAT- 2018/11/07 06:00
MHDA- 2020/02/25 06:00
PMCR- 2020/02/01
CRDT- 2018/11/07 06:00
PHST- 2018/05/25 00:00 [received]
PHST- 2018/07/30 00:00 [revised]
PHST- 2018/08/01 00:00 [accepted]
PHST- 2018/11/07 06:00 [pubmed]
PHST- 2020/02/25 06:00 [medline]
PHST- 2018/11/07 06:00 [entrez]
PHST- 2020/02/01 00:00 [pmc-release]
AID - S1465-3249(18)30562-0 [pii]
AID - 10.1016/j.jcyt.2018.08.001 [doi]
PST - ppublish
SO  - Cytotherapy. 2019 Feb;21(2):212-223. doi: 10.1016/j.jcyt.2018.08.001. Epub 2018 
      Nov 2.