PMID- 32133731
OWN - NLM
STAT- MEDLINE
DCOM- 20200601
LR  - 20200601
IS  - 1349-7006 (Electronic)
IS  - 1347-9032 (Print)
IS  - 1347-9032 (Linking)
VI  - 111
IP  - 5
DP  - 2020 May
TI  - Non-clinical efficacy, safety and stable clinical cell processing of induced 
      pluripotent stem cell-derived anti-glypican-3 chimeric antigen 
      receptor-expressing natural killer/innate lymphoid cells.
PG  - 1478-1490
LID - 10.1111/cas.14374 [doi]
AB  - The use of allogeneic, pluripotent stem-cell-derived immune cells for cancer 
      immunotherapy has been the subject of recent clinical trials. In Japan, 
      investigator-initiated clinical trials will soon begin for ovarian cancer 
      treatment using human leukocyte antigen (HLA)-homozygous-induced pluripotent stem 
      cell (iPSC)-derived anti-glypican-3 (GPC3) chimeric antigen receptor 
      (CAR)-expressing natural killer/innate lymphoid cells (NK/ILC). Using pluripotent 
      stem cells as the source for allogeneic immune cells facilitates stringent 
      quality control of the final product, in terms of efficacy, safety and 
      producibility. In this paper, we describe our methods for the stable, feeder-free 
      production of CAR-expressing NK/ILC cells from CAR-transduced iPSC with 
      clinically relevant scale and materials. The average number of cells that could 
      be differentiated from 1.8-3.6 x 10(6) iPSC within 7 weeks was 1.8-4.0 x 10(9) . 
      These cells showed stable CD45/CD7/CAR expression, effector functions of 
      cytotoxicity and interferon gamma (IFN-gamma) production against GPC3-expressing 
      tumor cells. When the CAR-NK/ILC cells were injected into a GPC3-positive, 
      ovarian-tumor-bearing, immunodeficient mouse model, we observed a significant 
      therapeutic effect that prolonged the survival of the animals. When the cells 
      were injected into immunodeficient mice during non-clinical safety tests, no 
      acute systemic toxicity or tumorigenicity of the final product or residual iPSC 
      was observed. In addition, our test results for the CAR-NK/ILC cells generated 
      with clinical manufacturing standards are encouraging, and these methods should 
      accelerate the development of allogeneic pluripotent stem cell-based immune cell 
      cancer therapies.
CI  - (c) 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd 
      on behalf of Japanese Cancer Association.
FAU - Ueda, Tatsuki
AU  - Ueda T
AD  - Shin Kaneko Laboratory, Department of Cell growth and Differentiation, Center for 
      iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
FAU - Kumagai, Ayako
AU  - Kumagai A
AD  - Shin Kaneko Laboratory, Department of Cell growth and Differentiation, Center for 
      iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
FAU - Iriguchi, Shoichi
AU  - Iriguchi S
AD  - Shin Kaneko Laboratory, Department of Cell growth and Differentiation, Center for 
      iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
FAU - Yasui, Yutaka
AU  - Yasui Y
AD  - Shin Kaneko Laboratory, Department of Cell growth and Differentiation, Center for 
      iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
AD  - Thyas Co. Ltd, Kyoto, Japan.
FAU - Miyasaka, Tadayo
AU  - Miyasaka T
AD  - Shin Kaneko Laboratory, Department of Cell growth and Differentiation, Center for 
      iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
FAU - Nakagoshi, Kengo
AU  - Nakagoshi K
AD  - Shin Kaneko Laboratory, Department of Cell growth and Differentiation, Center for 
      iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
FAU - Nakane, Kazuki
AU  - Nakane K
AD  - Shin Kaneko Laboratory, Department of Cell growth and Differentiation, Center for 
      iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
FAU - Saito, Keigo
AU  - Saito K
AD  - Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical 
      Trial Center, National Cancer Center, Kashiwa, Japan.
FAU - Takahashi, Mari
AU  - Takahashi M
AD  - Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical 
      Trial Center, National Cancer Center, Kashiwa, Japan.
FAU - Sasaki, Aki
AU  - Sasaki A
AD  - Department of Life Science Frontiers, Center for iPS Cell Research and 
      Application (CiRA), Kyoto University, Kyoto, Japan.
FAU - Yoshida, Shinsuke
AU  - Yoshida S
AD  - Department of Life Science Frontiers, Center for iPS Cell Research and 
      Application (CiRA), Kyoto University, Kyoto, Japan.
FAU - Takasu, Naoko
AU  - Takasu N
AD  - Department of Life Science Frontiers, Center for iPS Cell Research and 
      Application (CiRA), Kyoto University, Kyoto, Japan.
FAU - Seno, Hiroshi
AU  - Seno H
AD  - Department of Gastroenterology and Hepatology, Kyoto University Graduate School 
      of Medicine, Kyoto, Japan.
FAU - Uemura, Yasushi
AU  - Uemura Y
AD  - Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical 
      Trial Center, National Cancer Center, Kashiwa, Japan.
FAU - Tamada, Koji
AU  - Tamada K
AD  - Department of Immunology, Yamaguchi University Graduate School of Medicine, 
      Yamaguchi, Japan.
FAU - Nakatsura, Tetsuya
AU  - Nakatsura T
AUID- ORCID: 0000-0003-3918-2385
AD  - Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical 
      Trial Center, National Cancer Center, Kashiwa, Japan.
FAU - Kaneko, Shin
AU  - Kaneko S
AUID- ORCID: 0000-0003-2291-4586
AD  - Shin Kaneko Laboratory, Department of Cell growth and Differentiation, Center for 
      iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
LA  - eng
GR  - 15H04655/the Ministry of Education, Culture, Sports, Science and Technology 
      Japan/
GR  - 25293226/the Ministry of Education, Culture, Sports, Science and Technology 
      Japan/
GR  - 26293357/the Ministry of Education, Culture, Sports, Science and Technology 
      Japan/
GR  - Japan Agency for Medical Research and Development/
GR  - National Cancer Center Research Fund/
PT  - Journal Article
DEP - 20200331
PL  - England
TA  - Cancer Sci
JT  - Cancer science
JID - 101168776
RN  - 0 (GPC3 protein, human)
RN  - 0 (Glypicans)
RN  - 0 (Receptors, Chimeric Antigen)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Cell Differentiation
MH  - Cell Survival
MH  - Cytotoxicity, Immunologic
MH  - Disease Models, Animal
MH  - Female
MH  - Glypicans/genetics/*immunology/metabolism
MH  - Humans
MH  - Immunity, Innate
MH  - Immunotherapy, Adoptive
MH  - Induced Pluripotent Stem Cells/cytology/*immunology/metabolism
MH  - Interferon-gamma/immunology
MH  - Killer Cells, Natural/cytology/*immunology/transplantation
MH  - Lymphocyte Transfusion
MH  - Lymphocytes/cytology/*immunology
MH  - Mice
MH  - Mice, SCID
MH  - Ovarian Neoplasms/metabolism/pathology/therapy
MH  - Receptors, Chimeric Antigen/genetics/*immunology/metabolism
PMC - PMC7226201
OTO - NOTNLM
OT  - GPC3
OT  - ILC
OT  - NK
OT  - chimeric antigen receptor
OT  - iPSC
OT  - immunotherapy
COIS- Shin Kaneko is a founder, shareholder and chief scientific officer at Thyas and 
      received research funding from Takeda Pharmaceutical, Kirin Holdings, Terumo, 
      Tosoh, Sumitomo Chemical and Thyas. Tetsuya Nakatsura is a shareholder at Killer 
      T Save You. Koji Tamada is a shareholder of Noile-Immune Biotech and receives 
      consulting fees and research funding from Noile-Immune Biotech. Yutaka Yasui is 
      an employee of Thyas. The remaining authors declare no competing financial 
      interests.
EDAT- 2020/03/07 06:00
MHDA- 2020/06/02 06:00
PMCR- 2020/05/01
CRDT- 2020/03/06 06:00
PHST- 2019/11/28 00:00 [received]
PHST- 2020/02/07 00:00 [revised]
PHST- 2020/02/08 00:00 [accepted]
PHST- 2020/03/07 06:00 [pubmed]
PHST- 2020/06/02 06:00 [medline]
PHST- 2020/03/06 06:00 [entrez]
PHST- 2020/05/01 00:00 [pmc-release]
AID - CAS14374 [pii]
AID - 10.1111/cas.14374 [doi]
PST - ppublish
SO  - Cancer Sci. 2020 May;111(5):1478-1490. doi: 10.1111/cas.14374. Epub 2020 Mar 31.