PMID- 33717142
OWN - NLM
STAT- MEDLINE
DCOM- 20211004
LR  - 20240503
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 12
DP  - 2021
TI  - GMP-Compliant Universal Antigen Presenting Cells (uAPC) Promote the Metabolic 
      Fitness and Antitumor Activity of Armored Cord Blood CAR-NK Cells.
PG  - 626098
LID - 10.3389/fimmu.2021.626098 [doi]
LID - 626098
AB  - Natural killer (NK) cells are innate lymphocytes recognized for their important 
      role against tumor cells. NK cells expressing chimeric antigen receptors (CARs) 
      have enhanced effector function against various type of cancer and are attractive 
      contenders for the next generation of cancer immunotherapies. However, a number 
      of factors have hindered the application of NK cells for cellular therapy, 
      including their poor in vitro growth kinetics and relatively low starting 
      percentages within the mononuclear cell fraction of peripheral blood or cord 
      blood (CB). To overcome these limitations, we genetically-engineered human 
      leukocyte antigen (HLA)-A(-) and HLA-B(-) K562 cells to enforce the expression of 
      CD48, 4-1BBL, and membrane-bound IL-21 (mbIL21), creating a universal antigen 
      presenting cell (uAPC) capable of stimulating their cognate receptors on NK 
      cells. We have shown that uAPC can drive the expansion of both non-transduced 
      (NT) and CAR-transduced CB derived NK cells by >900-fold in 2 weeks of co-culture 
      with excellent purity (>99.9%) and without indications of senescence/exhaustion. 
      We confirmed that uAPC-expanded research- and clinical-grade NT and 
      CAR-transduced NK cells have higher metabolic fitness and display enhanced 
      effector function against tumor targets compared to the corresponding cell 
      fractions cultured without uAPCs. This novel approach allowed the expansion of 
      highly pure GMP-grade CAR NK cells at optimal cell numbers to be used for 
      adoptive CAR NK cell-based cancer immunotherapy.
CI  - Copyright (c) 2021 Liu, Ang, Kerbauy, Basar, Kaur, Kaplan, Li, Tong, Daher, Ensley, 
      Uprety, Nunez Cortes, Yang, Li, Shaim, Reyes Silva, Lin, Mohanty, Acharya, 
      Shanley, Muniz-Feliciano, Banerjee, Chen, Champlin, Shpall and Rezvani.
FAU - Liu, Enli
AU  - Liu E
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, Houston, TX, United States.
FAU - Ang, Sonny O T
AU  - Ang SOT
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, Houston, TX, United States.
FAU - Kerbauy, Lucila
AU  - Kerbauy L
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, Houston, TX, United States.
AD  - Departments of Stem Cell Transplantation and Hemotherapy/Cellular Therapy, 
      Hospital Israelita Albert Einstein, Sao Paulo, Brazil.
AD  - Department of Genetics and Evolutionary Biology, Human Genome and Stem Cell 
      Research Center, Biosciences Institute, University of Sao Paulo, Sao Paulo, 
      Brazil.
FAU - Basar, Rafet
AU  - Basar R
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, Houston, TX, United States.
FAU - Kaur, Indreshpal
AU  - Kaur I
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, Houston, TX, United States.
FAU - Kaplan, Mecit
AU  - Kaplan M
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, Houston, TX, United States.
FAU - Li, Li
AU  - Li L
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, Houston, TX, United States.
FAU - Tong, Yijiu
AU  - Tong Y
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, Houston, TX, United States.
FAU - Daher, May
AU  - Daher M
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, Houston, TX, United States.
FAU - Ensley, Emily L
AU  - Ensley EL
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, Houston, TX, United States.
FAU - Uprety, Nadima
AU  - Uprety N
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, Houston, TX, United States.
FAU - Nunez Cortes, Ana Karen
AU  - Nunez Cortes AK
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, Houston, TX, United States.
FAU - Yang, Ryan Z
AU  - Yang RZ
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, Houston, TX, United States.
FAU - Li, Ye
AU  - Li Y
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, Houston, TX, United States.
FAU - Shaim, Hila
AU  - Shaim H
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, Houston, TX, United States.
FAU - Reyes Silva, Francia
AU  - Reyes Silva F
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, Houston, TX, United States.
FAU - Lin, Paul
AU  - Lin P
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, Houston, TX, United States.
FAU - Mohanty, Vakul
AU  - Mohanty V
AD  - Department of Bioinformatics and Computational Biology, The University of Texas 
      MD Anderson Cancer Center, Houston, TX, United States.
FAU - Acharya, Sunil
AU  - Acharya S
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, Houston, TX, United States.
FAU - Shanley, Mayra
AU  - Shanley M
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, Houston, TX, United States.
FAU - Muniz-Feliciano, Luis
AU  - Muniz-Feliciano L
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, Houston, TX, United States.
FAU - Banerjee, Pinaki P
AU  - Banerjee PP
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, Houston, TX, United States.
FAU - Chen, Ken
AU  - Chen K
AD  - Department of Bioinformatics and Computational Biology, The University of Texas 
      MD Anderson Cancer Center, Houston, TX, United States.
FAU - Champlin, Richard E
AU  - Champlin RE
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, Houston, TX, United States.
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, United States.
FAU - Rezvani, Katayoun
AU  - Rezvani K
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, Houston, TX, United States.
LA  - eng
GR  - P30 CA016672/CA/NCI NIH HHS/United States
GR  - P50 CA100632/CA/NCI NIH HHS/United States
GR  - R01 CA211044/CA/NCI NIH HHS/United States
GR  - P01 CA148600/CA/NCI NIH HHS/United States
GR  - T32 CA009666/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20210226
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (HLA Antigens)
RN  - 0 (Receptors, Chimeric Antigen)
RN  - 0 (Receptors, Natural Killer Cell)
SB  - IM
MH  - Animals
MH  - Antigen-Presenting Cells/*metabolism
MH  - Cell Engineering
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Cytotoxicity, Immunologic
MH  - Fetal Blood
MH  - HLA Antigens/genetics
MH  - Humans
MH  - K562 Cells
MH  - Killer Cells, Natural/*immunology/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Receptors, Chimeric Antigen/*genetics
MH  - Receptors, Natural Killer Cell/metabolism
MH  - Transcriptome
MH  - Transduction, Genetic
MH  - Xenograft Model Antitumor Assays
PMC - PMC7952299
OTO - NOTNLM
OT  - K562 cells
OT  - NK cell expansion
OT  - adoptive cancer immunotherapy
OT  - cell engineering
OT  - universal antigen presenting cell
COIS- KR, ES, RC, EL, SAn, RB, MD, PB, and The University of Texas MD Anderson Cancer 
      Center (MDACC) have an institutional financial conflict of interest with Takeda 
      Pharmaceutical for the licensing of the technology related to CAR-NK cell 
      research reported here. MD Anderson has implemented an Institutional Conflict of 
      Interest Management and Monitoring Plan to manage and monitor the conflict of 
      interest with respect to MDACC's conduct of any other ongoing or future research 
      related to this relationship. KR, ES, RB, EL, SAn and The University of Texas MD 
      Anderson Cancer Center has an institutional financial conflict of interest with 
      Affimed GmbH. Because MD Anderson is committed to the protection of human 
      subjects and the effective management of its financial conflicts of interest in 
      relation to its research activities, MD Anderson is implementing an Institutional 
      Conflict of Interest Management and Monitoring Plan to manage and monitor the 
      conflict of interest with respect to MD Anderson's conduct of any other ongoing 
      or future research related to this relationship. KR participates on Scientific 
      Advisory Board for GemoAb, AvengeBio, Kiadis, GSK and Bayer. The remaining 
      authors declare that the research was conducted in the absence of any commercial 
      or financial relationships that could be construed as a potential conflict of 
      interest.
EDAT- 2021/03/16 06:00
MHDA- 2021/10/05 06:00
PMCR- 2021/01/01
CRDT- 2021/03/15 06:58
PHST- 2020/11/04 00:00 [received]
PHST- 2021/01/26 00:00 [accepted]
PHST- 2021/03/15 06:58 [entrez]
PHST- 2021/03/16 06:00 [pubmed]
PHST- 2021/10/05 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2021.626098 [doi]
PST - epublish
SO  - Front Immunol. 2021 Feb 26;12:626098. doi: 10.3389/fimmu.2021.626098. eCollection 
      2021.