Enhanced Expression of Anti-CD19 Chimeric Antigen Receptor in Transposon-Engineered T Cells

Overview

Journal Mol Ther Methods Clin Dev

Publisher Cell Press

Date 2018 Apr 25

PMID 29687032

Citations 38

Authors

Daisuke Morita

Nobuhiro Nishio

Shoji Saito

Miyuki Tanaka

Nozomu Kawashima

Yusuke Okuno

Satoshi Suzuki

Kazuyuki Matsuda

Yasuhiro Maeda

Matthew H Wilson

Gianpietro Dotti

Cliona M Rooney

Yoshiyuki Takahashi

Yozo Nakazawa

Affiliations

Soon will be listed here.

Abstract

Adoptive T cell therapy using chimeric antigen receptor (CAR)-modified T cells is a promising cancer immunotherapy. We previously developed a non-viral method of gene transfer into T cells using a transposon system to improve the cost-effectiveness of CAR-T cell therapy. Here, we have further improved our technology by a novel culture strategy to increase the transfection efficiency and to reduce the time of T cell manufacturing. Using a CH2CH3-free CD19-specific CAR transposon vector and combining irradiated activated T cells (ATCs) as feeder cells and virus-specific T cell receptor (TCR) stimulation, we achieved 51.4% ± 14% CAR T cells and 2.8-fold expansion after 14 culture days. Expanded CD19.CAR-T cells maintained a significant fraction of CD45RACCR7 T cells and demonstrated potent antitumor activity against CD19 leukemic cells both and . Therefore, -based gene transfer may provide an alternative to viral gene transfer for CAR-T cell therapy.

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