Engineering light-controllable CAR T cells for cancer immunotherapy.

Science Advances
Ziliang HuangYingxiao Wang

Abstract

T cells engineered to express chimeric antigen receptors (CARs) can recognize and engage with target cancer cells with redirected specificity for cancer immunotherapy. However, there is a lack of ideal CARs for solid tumor antigens, which may lead to severe adverse effects. Here, we developed a light-inducible nuclear translocation and dimerization (LINTAD) system for gene regulation to control CAR T activation. We first demonstrated light-controllable gene expression and functional modulation in human embryonic kidney 293T and Jurkat T cell lines. We then improved the LINTAD system to achieve optimal efficiency in primary human T cells. The results showed that pulsed light stimulations can activate LINTAD CAR T cells with strong cytotoxicity against target cancer cells, both in vitro and in vivo. Therefore, our LINTAD system can serve as an efficient tool to noninvasively control gene activation and activate inducible CAR T cells for precision cancer immunotherapy.

References

Dec 8, 2004·Nature Biotechnology·Stéphanie CabantousGeoffrey S Waldo
Feb 25, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·Richard A MorganSteven A Rosenberg
Nov 3, 2010·Nature Methods·Matthew J KennedyChandra L Tucker
Jun 1, 2013·Science·Kipp WeiskopfK Christopher Garcia
Aug 22, 2013·Chemical Communications : Chem Comm·Konrad MüllerWilfried Weber
Sep 3, 2013·Nature Methods·Raik GrünbergLuis Serrano
Dec 18, 2013·Science Translational Medicine·Victor D FedorovMichel Sadelain
Mar 29, 2014·The Cancer Journal·Carlos A RamosGianpietro Dotti
Jun 21, 2014·Cell Death and Differentiation·J LemkeH Walczak
Feb 11, 2015·Nature Chemical Biology·Lauren R Polstein, Charles A Gersbach
Mar 3, 2015·Nature Methods·Alejandro ChavezGeorge M Church
Apr 12, 2016·Nature Chemical Biology·Amir TaslimiChandra L Tucker
Apr 17, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Marcela V Maus, Carl H June
Apr 19, 2016·Nature Chemical Biology·Hayretin YumerefendiBrian Kuhlman
May 10, 2016·Nature Methods·Andrii A KaberniukVladislav V Verkhusha
Mar 28, 2017·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jonathan FisherJohn Anderson
Sep 17, 2017·Nature Communications·Liting DuanBianxiao Cui
Jan 19, 2018·Annual Review of Biomedical Engineering·Matthew J BrennerWilson W Wong
Sep 22, 2018·Science·Xiaojing J GaoMichael B Elowitz
Nov 11, 2018·British Journal of Cancer·Nicholas TokarewSebastian Kobold
Apr 3, 2019·Frontiers in Bioengineering and Biotechnology·Fabio CaliendoVelia Siciliano

❮ Previous
Next ❯

Citations

Jul 14, 2020·Biochemical Society Transactions·Denis HartmannMichael J Booth
Oct 6, 2020·Frontiers in Immunology·María Tristán-ManzanoFrancisco Martin
Aug 23, 2020·Cancers·Leonardo ChicaybamBryan E Strauss
Aug 9, 2020·Cancers·Thomas J GardnerDavid Scheinberg
Jan 14, 2021·Nature Nanotechnology·Ningqiang GongMichael J Mitchell
Feb 7, 2021·Biosensors & Bioelectronics·Jia YangLianqing Liu
Dec 22, 2020·Advanced Science·Rui LiWeiqiang Chen
Feb 20, 2021·Nature Reviews. Genetics·Gavin I EllisJames L Riley
Feb 26, 2021·Proceedings of the National Academy of Sciences of the United States of America·Geoff P O'DonoghueWendell A Lim
Apr 17, 2021·Advanced Materials·Arun R K KumarAndy Tay
May 1, 2021·International Journal of Molecular Sciences·Benjamin CaulierSébastien Wälchli
May 1, 2021·International Journal of Molecular Sciences·Jong-Bok LeeLi Zhang
May 8, 2021·Nature Chemical Biology·Lian HeYubin Zhou
Jun 9, 2021·Nature Communications·Maysam MansouriMartin Fussenegger
May 25, 2021·Bioengineering & Translational Medicine·Lily Li-Wen WangSamir Mitragotri
Jul 4, 2021·Current Opinion in Chemical Biology·Oliver MaddersonMartin Fussenegger
Aug 15, 2021·Current Opinion in Immunology·Ali Can Sahillioglu, Ton N Schumacher
Aug 19, 2021·Proceedings of the National Academy of Sciences of the United States of America·Linfeng YangHaifeng Ye
Aug 29, 2021·Pharmaceutics·Giovanna C N B LôboSônia N Báo
Oct 8, 2021·Nature Reviews. Drug Discovery·Andres Cubillos-RuizJose M Lora

❮ Previous
Next ❯

Methods Mentioned

BETA
nuclear translocation
fluorescence
flow cytometry
transfection
ELISA
bioluminescence imaging
transfect
PCR
electrophoresis
Assay

Software Mentioned

Living Image
LINTAD
Nearpow
synNotch
CRY2PHR
MetaFluor

Related Concepts

Related Feeds

Cancer Vaccines

Cancer vaccines are vaccines that either treat existing cancer or prevent development of a cancer.