Non-clinical efficacy, safety, and stable clinical cell processing of iPSC-derived anti-GPC3 CAR-expressing NK/ILC cells

Cancer Science
Tatsuki UedaShin Kaneko

Abstract

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 iPSCs with clinically relevant scale and materials. The average number of cells that could be differentiated from 1.8-3.6 x 106 iPSC within 7 weeks was 1.8-4.0 x 109 . These cells showed stable CD45/CD7/CAR expression, effector functions of cytotoxicity, and IFN-γ 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 ...Continue Reading

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Citations

Jun 20, 2020·Scandinavian Journal of Immunology·Emmanuelle BenardSébastien Wälchli
Sep 19, 2020·Development·Hideyuki Okano, Doug Sipp
Jan 26, 2021·Frontiers in Immunology·Kenneth J CaldwellAimee C Talleur
Jan 8, 2021·Journal of Hematology & Oncology·Sizhe LiuJennifer Wu
Feb 2, 2021·Frontiers in Oncology·Franklin NingChristina M Annunziata
Apr 4, 2021·International Journal of Molecular Sciences·Katarzyna M TerlikowskaSławomir J Terlikowski
Apr 21, 2021·British Journal of Haematology·Sergio QuerolAlejandro Madrigal
May 3, 2021·Journal of Hematology & Oncology·Ying GongWilfred T V Germeraad
Jun 29, 2021·Frontiers in Oncology·Faroogh MarofiMostafa Jarahian
May 30, 2021·Cancer Science·Faroogh MarofiMostafa Jarahian
Aug 10, 2021·Frontiers in Immunology·Olga ZimmermannovaCarlos-Filipe Pereira
Aug 11, 2021·Molecules and Cells·Peter Karagiannis, Shin-Il Kim
Sep 21, 2021·Expert Opinion on Biological Therapy·Mina HosseiniNima Rezaei

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Methods Mentioned

BETA
ELISA
PCR
Pulldown
chip
flow cytometry
transfection
phage display
xenograft
FACS
genetic modification

Clinical Trials Mentioned

NCT02395250

Software Mentioned

Biacore X100
Biacore X100 evaluation
FlowJo Star

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