PMID- 29515236
OWN - NLM
STAT- MEDLINE
DCOM- 20190401
LR  - 20210103
IS  - 1476-5551 (Electronic)
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 32
IP  - 6
DP  - 2018 Jun
TI  - Compound CAR T-cells as a double-pronged approach for treating acute myeloid 
      leukemia.
PG  - 1317-1326
LID - 10.1038/s41375-018-0075-3 [doi]
AB  - Acute myeloid leukemia (AML) bears heterogeneous cells that can consequently 
      offset killing by single-CAR-based therapy, which results in disease relapse. 
      Leukemic stem cells (LSCs) associated with CD123 expression comprise a rare 
      population that also plays an important role in disease progression and relapse. 
      Here, we report on the robust anti-tumor activity of a compound CAR (cCAR) T-cell 
      possessing discrete scFv domains targeting two different AML antigens, CD123, and 
      CD33, simultaneously. We determined that the resulting cCAR T-cells possessed 
      consistent, potent, and directed cytotoxicity against each target antigen 
      population. Using four leukemia mouse models, we found superior in vivo survival 
      after cCAR treatment. We also designed an alemtuzumab safety-switch that allowed 
      for rapid cCAR therapy termination in vivo. These findings indicate that 
      targeting both CD123 and CD33 on AML cells may be an effective strategy for 
      eliminating both AML bulk disease and LSCs, and potentially prevent relapse due 
      to antigen escape or LSC persistence.
FAU - Petrov, Jessica C
AU  - Petrov JC
AD  - iCell Gene Therapeutics LLC Research & Development Division Long Island High 
      Technology Incubator, 25 Health Science Drive, Stony Brook, NY, 11790, USA.
FAU - Wada, Masayuki
AU  - Wada M
AD  - iCell Gene Therapeutics LLC Research & Development Division Long Island High 
      Technology Incubator, 25 Health Science Drive, Stony Brook, NY, 11790, USA. 
      masayuki.wada@icellgene.com.
FAU - Pinz, Kevin G
AU  - Pinz KG
AD  - iCell Gene Therapeutics LLC Research & Development Division Long Island High 
      Technology Incubator, 25 Health Science Drive, Stony Brook, NY, 11790, USA.
FAU - Yan, Lulu E
AU  - Yan LE
AD  - iCell Gene Therapeutics LLC Research & Development Division Long Island High 
      Technology Incubator, 25 Health Science Drive, Stony Brook, NY, 11790, USA.
FAU - Chen, Kevin H
AU  - Chen KH
AD  - iCell Gene Therapeutics LLC Research & Development Division Long Island High 
      Technology Incubator, 25 Health Science Drive, Stony Brook, NY, 11790, USA.
FAU - Shuai, Xiao
AU  - Shuai X
AD  - Department of Hematology West China Hospital, Sichuan University, Chengdu, P.R. 
      China.
FAU - Liu, Hua
AU  - Liu H
AD  - Department of Pathology, Stony Brook Medicine, Stony Brook, NY, 11794, USA.
FAU - Chen, Xi
AU  - Chen X
AD  - Macau Institute for Applied Research in Medicine and Health, Macau University of 
      Science and Technology, Macau, China.
FAU - Leung, Lai-Han
AU  - Leung LH
AD  - Macau Institute for Applied Research in Medicine and Health, Macau University of 
      Science and Technology, Macau, China.
FAU - Salman, Huda
AU  - Salman H
AD  - Department of Internal Medicine Stony Brook Medicine, Stony Brook University 
      Medical Center, Stony Brook, NY, 11794, USA.
FAU - Hagag, Nabil
AU  - Hagag N
AD  - Department of Internal Medicine Stony Brook Medicine, Stony Brook University 
      Medical Center, Stony Brook, NY, 11794, USA.
FAU - Liu, Fang
AU  - Liu F
AD  - Department of Hematology, Chengdu Military General Hospital, Chengdu, Sichuan, 
      P.R. China.
FAU - Jiang, Xun
AU  - Jiang X
AD  - iCell Gene Therapeutics LLC Research & Development Division Long Island High 
      Technology Incubator, 25 Health Science Drive, Stony Brook, NY, 11790, USA.
FAU - Ma, Yupo
AU  - Ma Y
AD  - iCell Gene Therapeutics LLC Research & Development Division Long Island High 
      Technology Incubator, 25 Health Science Drive, Stony Brook, NY, 11790, USA. 
      yupo.ma@icellgene.com.
AD  - Department of Pathology, Stony Brook Medicine, Stony Brook, NY, 11794, USA. 
      yupo.ma@icellgene.com.
AD  - Macau Institute for Applied Research in Medicine and Health, Macau University of 
      Science and Technology, Macau, China. yupo.ma@icellgene.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180225
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Interleukin-3 Receptor alpha Subunit)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Sialic Acid Binding Ig-like Lectin 3)
RN  - 3A189DH42V (Alemtuzumab)
SB  - IM
MH  - Alemtuzumab/therapeutic use
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cytotoxicity, Immunologic
MH  - Humans
MH  - Immunotherapy, Adoptive/*methods
MH  - Interleukin-3 Receptor alpha Subunit/*antagonists & inhibitors
MH  - Leukemia, Myeloid, Acute/*therapy
MH  - Male
MH  - Mice
MH  - Receptors, Antigen, T-Cell/*immunology
MH  - Sialic Acid Binding Ig-like Lectin 3/*antagonists & inhibitors
PMC - PMC5990523
COIS- Yupo Ma is a co-founder of iCell Gene Therapeutics, LLC.
EDAT- 2018/03/09 06:00
MHDA- 2019/04/02 06:00
PMCR- 2018/02/25
CRDT- 2018/03/09 06:00
PHST- 2017/10/23 00:00 [received]
PHST- 2018/01/31 00:00 [accepted]
PHST- 2017/12/22 00:00 [revised]
PHST- 2018/03/09 06:00 [pubmed]
PHST- 2019/04/02 06:00 [medline]
PHST- 2018/03/09 06:00 [entrez]
PHST- 2018/02/25 00:00 [pmc-release]
AID - 10.1038/s41375-018-0075-3 [pii]
AID - 75 [pii]
AID - 10.1038/s41375-018-0075-3 [doi]
PST - ppublish
SO  - Leukemia. 2018 Jun;32(6):1317-1326. doi: 10.1038/s41375-018-0075-3. Epub 2018 Feb 
      25.