@article{7ec976aeeb454be39a53669c86ade0e1,
title = "Generation of hypoxia-sensing chimeric antigen receptor T cells",
abstract = "Exploiting hypoxia in solid malignancies to restrict expression of chimeric antigen receptors (CARs) on engineered T cells to the tumor microenvironment overcomes the risk of on-target off-tumor toxicity and minimizes tonic signaling, which promotes CAR T cell exhaustion. This protocol summarizes the synthetic biology underlying the development of a stringent oxygen-sensitive CAR for in vitro and in vivo preclinical characterization. For complete details on the use and execution of this protocol, please refer to Kosti et al. (2021).",
author = "Paris Kosti and {Larios Martinez}, Ileana and John Maher and James Arnold",
note = "Funding Information: This work was funded by the European Research Council ( 335326 ). P.K. was supported by the UK Medical Research Council ( MR/N013700/1 ) and was a KCL member of the MRC Doctoral Training Partnership in Biomedical Sciences. K.I.L.-M. is supported from Consejo Nacional de Ciencia y Tecnologia ( CONACyT ) and Leucid Bio . Research was also supported by the Cancer Research UK King{\textquoteright}s Health Partners Centre and Experimental Cancer Medicine Centre at King{\textquoteright}s College London , and the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King{\textquoteright}s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The authors thank Dr Adam Ajina (KCL) for taking blood samples, and Dr David M. Davies for reading the manuscript and helpful discussion. Funding Information: This work was funded by the European Research Council (335326). P.K. was supported by the UK Medical Research Council (MR/N013700/1) and was a KCL member of the MRC Doctoral Training Partnership in Biomedical Sciences. K.I.L.-M. is supported from Consejo Nacional de Ciencia y Tecnologia (CONACyT) and Leucid Bio. Research was also supported by the Cancer Research UK King's Health Partners Centre and Experimental Cancer Medicine Centre at King's College London, and the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The authors thank Dr Adam Ajina (KCL) for taking blood samples, and Dr David M. Davies for reading the manuscript and helpful discussion. P.K. K.I.L.-M. J.M. and J.N.A. designed and optimized the approach, interpreted the data, and wrote the protocol. J.M. is co-founder and chief scientific officer of Leucid Bio which is a spin-out company focused on development of cellular therapeutic agents. K.I.L.-M. is part funded by Leucid Bio. P.K. J.M. and J.N.A. are named inventors on a patent submitted in relation to this work. Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = sep,
day = "17",
doi = "10.1016/j.xpro.2021.100723",
language = "English",
volume = "2",
journal = "STAR Protocols",
issn = "2666-1667",
publisher = "Cell Press",
number = "3",
}
