A CAR RNA FISH assay to study functional and spatial heterogeneity of chimeric antigen receptor T cells in tissue

Abstract Chimeric antigen receptor (CAR) T cells are engineered cells used in cancer therapy and are studied to treat infectious diseases. Trafficking and persistence of CAR T cells is an important requirement for efficacy to target cancer. Here, we describe a CAR RNA FISH histo-cytometry platform c...

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Autores principales:	Karsten Eichholz, Alvason Zhenhua Li, Kurt Diem, Michael Claus Jensen, Jia Zhu, Lawrence Corey
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ce06e7f3a5eb43eba5951369f597b212
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spelling	oai:doaj.org-article:ce06e7f3a5eb43eba5951369f597b2122021-12-02T17:45:20ZA CAR RNA FISH assay to study functional and spatial heterogeneity of chimeric antigen receptor T cells in tissue10.1038/s41598-021-92196-x2045-2322https://doaj.org/article/ce06e7f3a5eb43eba5951369f597b2122021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92196-xhttps://doaj.org/toc/2045-2322Abstract Chimeric antigen receptor (CAR) T cells are engineered cells used in cancer therapy and are studied to treat infectious diseases. Trafficking and persistence of CAR T cells is an important requirement for efficacy to target cancer. Here, we describe a CAR RNA FISH histo-cytometry platform combined with a random reaction seed image analysis algorithm to quantitate spatial distribution and in vivo functional activity of a CAR T cell population at a single cell resolution for preclinical models. In situ, CAR T cell exhibited a heterogenous effector gene expression and this was related to the distance from tumor cells, allowing a quantitative assessment of the potential in vivo effectiveness. The platform offers the potential to study immune functions of genetically engineered cells in situ with their target cells in tissues with high statistical power and thus, can serve as an important tool for preclinical assessment of CAR T cell effectiveness.Karsten EichholzAlvason Zhenhua LiKurt DiemMichael Claus JensenJia ZhuLawrence CoreyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Karsten Eichholz Alvason Zhenhua Li Kurt Diem Michael Claus Jensen Jia Zhu Lawrence Corey A CAR RNA FISH assay to study functional and spatial heterogeneity of chimeric antigen receptor T cells in tissue
description	Abstract Chimeric antigen receptor (CAR) T cells are engineered cells used in cancer therapy and are studied to treat infectious diseases. Trafficking and persistence of CAR T cells is an important requirement for efficacy to target cancer. Here, we describe a CAR RNA FISH histo-cytometry platform combined with a random reaction seed image analysis algorithm to quantitate spatial distribution and in vivo functional activity of a CAR T cell population at a single cell resolution for preclinical models. In situ, CAR T cell exhibited a heterogenous effector gene expression and this was related to the distance from tumor cells, allowing a quantitative assessment of the potential in vivo effectiveness. The platform offers the potential to study immune functions of genetically engineered cells in situ with their target cells in tissues with high statistical power and thus, can serve as an important tool for preclinical assessment of CAR T cell effectiveness.
format	article
author	Karsten Eichholz Alvason Zhenhua Li Kurt Diem Michael Claus Jensen Jia Zhu Lawrence Corey
author_facet	Karsten Eichholz Alvason Zhenhua Li Kurt Diem Michael Claus Jensen Jia Zhu Lawrence Corey
author_sort	Karsten Eichholz
title	A CAR RNA FISH assay to study functional and spatial heterogeneity of chimeric antigen receptor T cells in tissue
title_short	A CAR RNA FISH assay to study functional and spatial heterogeneity of chimeric antigen receptor T cells in tissue
title_full	A CAR RNA FISH assay to study functional and spatial heterogeneity of chimeric antigen receptor T cells in tissue
title_fullStr	A CAR RNA FISH assay to study functional and spatial heterogeneity of chimeric antigen receptor T cells in tissue
title_full_unstemmed	A CAR RNA FISH assay to study functional and spatial heterogeneity of chimeric antigen receptor T cells in tissue
title_sort	car rna fish assay to study functional and spatial heterogeneity of chimeric antigen receptor t cells in tissue
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ce06e7f3a5eb43eba5951369f597b212
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A CAR RNA FISH assay to study functional and spatial heterogeneity of chimeric antigen receptor T cells in tissue

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