PMID- 26740053
OWN - NLM
STAT- MEDLINE
DCOM- 20160613
LR  - 20160203
IS  - 1873-5835 (Electronic)
IS  - 0145-2126 (Linking)
VI  - 41
DP  - 2016 Feb
TI  - CD123 redirected multiple virus-specific T cells for acute myeloid leukemia.
PG  - 76-84
LID - S0145-2126(15)30560-9 [pii]
LID - 10.1016/j.leukres.2015.12.003 [doi]
AB  - Hematopoietic stem cell transplantation (HSCT) has been increasingly used as a 
      curative treatment for acute myeloid leukemia (AML). However, relapse rates after 
      HSCT in complete remission (CR) are reported between 30% and 70%. In addition, 
      numerous studies suggested that secondary viral infection from a variety of 
      viruses including Epstein-Barr virus (EBV), adenovirus (Adv), and cytomegalovirus 
      (CMV) are among the most common causes of death post-HSCT. Currently, chimeric 
      antigen receptor (CAR)-based T cells have been developed to treat AML in clinical 
      studies, while virus-specific cytotoxic T cells (VST) have been proven to be able 
      to effectively prevent or treat viral infection after HSCT. Thus it would be 
      desirable to develop T cells with the ability of simultaneously targeting AML 
      relapse and viral infection. In this article, we now describe the generation of 
      VST cells that are engineered to express CAR for a specific AML cell-surface 
      antigen CD123 (CD123-CAR-VST). Using Dendritic cells (DCs) pulsed with EBV, Adv, 
      and CMV peptides as sources of viral antigens, we generated VST from A2 donor 
      peripheral mononuclear cells (PBMC). VST were then transduced with retroviral 
      vector encoding CD123-CAR to generate CD123-CAR-VST. We demonstrated that 
      CD123-CAR-VST recognized EBV, Adv, and CMV epitopes and had HLA-restricted 
      virus-specific cytotoxic effector function against EBV target. In addition, 
      CD123-CAR-VST retained the specificity against CD123-positive AML cell lines such 
      as MOLM13 and THP-1 in vitro. Thus our results suggested that CD123-CAR-VST might 
      be a valuable candidate to simultaneously prevent or treat relapse and viral 
      infection in AML HSCT recipients.
CI  - Copyright (c) 2015 Elsevier Ltd. All rights reserved.
FAU - Zhou, Li
AU  - Zhou L
AD  - Shangdong University, Jinan, Shandong, PR China; Department of Hematology, Anhui 
      Provincial Hospital, Hefei, Anhui, PR China; Center for Cell and Gene Therapy, 
      Texas Children's Hospital, Houston Methodist Hospital, Baylor College of 
      Medicine, Houston, TX, USA.
FAU - Liu, Xin
AU  - Liu X
AD  - Department of Hematology, Anhui Provincial Hospital, Hefei, Anhui, PR China.
FAU - Wang, Xingbing
AU  - Wang X
AD  - Department of Hematology, Anhui Provincial Hospital, Hefei, Anhui, PR China.
FAU - Sun, Zimin
AU  - Sun Z
AD  - Shangdong University, Jinan, Shandong, PR China; Department of Hematology, Anhui 
      Provincial Hospital, Hefei, Anhui, PR China. Electronic address: 
      zmsun_vip@163.com.
FAU - Song, Xiao-Tong
AU  - Song XT
AD  - Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist 
      Hospital, Baylor College of Medicine, Houston, TX, USA; Department of Pathology 
      and Immunology, Baylor College of Medicine, Houston, TX, USA. Electronic address: 
      xsong1@bcm.edu.
LA  - eng
GR  - R01CA148748/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20151219
PL  - England
TA  - Leuk Res
JT  - Leukemia research
JID - 7706787
RN  - 0 (Antigens, Viral)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Antiviral Agents)
RN  - 0 (IL3RA protein, human)
RN  - 0 (Interleukin-3 Receptor alpha Subunit)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Recombinant Fusion Proteins)
SB  - IM
MH  - Antigens, Viral/immunology
MH  - Antineoplastic Agents/*immunology
MH  - Antiviral Agents/*immunology
MH  - Cell Separation
MH  - Enzyme-Linked Immunospot Assay
MH  - Hematopoietic Stem Cell Transplantation/adverse effects
MH  - Humans
MH  - Immunophenotyping
MH  - Immunotherapy, Adoptive/*methods
MH  - Interleukin-3 Receptor alpha Subunit/*immunology
MH  - Leukemia, Myeloid, Acute/*immunology
MH  - Receptors, Antigen, T-Cell/immunology
MH  - Recombinant Fusion Proteins/immunology
MH  - T-Lymphocytes, Cytotoxic/*immunology
MH  - Virus Diseases/immunology
OTO - NOTNLM
OT  - Acute myeloid leukemia
OT  - CD123
OT  - Chimeric antigen receptor
OT  - Virus-specific cytotoxic T cells
EDAT- 2016/01/08 06:00
MHDA- 2016/06/14 06:00
CRDT- 2016/01/08 06:00
PHST- 2015/07/23 00:00 [received]
PHST- 2015/11/16 00:00 [revised]
PHST- 2015/12/14 00:00 [accepted]
PHST- 2016/01/08 06:00 [entrez]
PHST- 2016/01/08 06:00 [pubmed]
PHST- 2016/06/14 06:00 [medline]
AID - S0145-2126(15)30560-9 [pii]
AID - 10.1016/j.leukres.2015.12.003 [doi]
PST - ppublish
SO  - Leuk Res. 2016 Feb;41:76-84. doi: 10.1016/j.leukres.2015.12.003. Epub 2015 Dec 
      19.