Implementing Logic Gates for Safer Immunotherapy of Cancer

Targeting solid tumors with absolute precision is a long-standing challenge in cancer immunotherapy. The identification of antigens, which are expressed by a large fraction of tumors of a given type and, preferably, across various types, but not by normal cells, holds the key to developing safe, off...

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Autores principales:	Mohammed Azharuddin Savanur, Hadas Weinstein-Marom, Gideon Gross
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Boolean logic gates adoptive cell therapy chimeric antigen receptors on-target off-tumor toxicity synthetic biology Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/23442c29f58341b58f7775efe91e8b45
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id	oai:doaj.org-article:23442c29f58341b58f7775efe91e8b45
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spelling	oai:doaj.org-article:23442c29f58341b58f7775efe91e8b452021-11-04T11:47:39ZImplementing Logic Gates for Safer Immunotherapy of Cancer1664-322410.3389/fimmu.2021.780399https://doaj.org/article/23442c29f58341b58f7775efe91e8b452021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.780399/fullhttps://doaj.org/toc/1664-3224Targeting solid tumors with absolute precision is a long-standing challenge in cancer immunotherapy. The identification of antigens, which are expressed by a large fraction of tumors of a given type and, preferably, across various types, but not by normal cells, holds the key to developing safe, off-the-shelf immunotherapies. Although the quest for widely shared, strictly tumor-specific antigens has been the focus of tremendous effort, only few such candidates have been implicated. Almost all antigens that are currently explored as targets for chimeric antigen receptor (CAR) or T cell receptor (TCR)-T cell therapy are also expressed by healthy cells and the risk of on-target off-tumor toxicity has remained a major concern. Recent studies suggest that this risk could be obviated by targeting instead combinations of two or more antigens, which are co-expressed by tumor but not normal cells and, as such, are tumor-specific. Moreover, the expression of a shared tumor antigen along with the lack of a second antigen that is expressed by normal tissues can also be exploited for precise recognition. Additional cues, antigenic or non-antigenic ones, which characterize the tumor microenvironment, could be harnessed to further increase precision. This review focuses on attempts to define the targetable signatures of tumors and assesses different strategies employing advanced synthetic biology for translating such information into safer modes of immunotherapy, implementing the principles of Boolean logic gates.Mohammed Azharuddin SavanurMohammed Azharuddin SavanurHadas Weinstein-MaromHadas Weinstein-MaromGideon GrossGideon GrossFrontiers Media S.A.articleBoolean logic gatesadoptive cell therapychimeric antigen receptorson-target off-tumor toxicitysynthetic biologyImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Boolean logic gates adoptive cell therapy chimeric antigen receptors on-target off-tumor toxicity synthetic biology Immunologic diseases. Allergy RC581-607
spellingShingle	Boolean logic gates adoptive cell therapy chimeric antigen receptors on-target off-tumor toxicity synthetic biology Immunologic diseases. Allergy RC581-607 Mohammed Azharuddin Savanur Mohammed Azharuddin Savanur Hadas Weinstein-Marom Hadas Weinstein-Marom Gideon Gross Gideon Gross Implementing Logic Gates for Safer Immunotherapy of Cancer
description	Targeting solid tumors with absolute precision is a long-standing challenge in cancer immunotherapy. The identification of antigens, which are expressed by a large fraction of tumors of a given type and, preferably, across various types, but not by normal cells, holds the key to developing safe, off-the-shelf immunotherapies. Although the quest for widely shared, strictly tumor-specific antigens has been the focus of tremendous effort, only few such candidates have been implicated. Almost all antigens that are currently explored as targets for chimeric antigen receptor (CAR) or T cell receptor (TCR)-T cell therapy are also expressed by healthy cells and the risk of on-target off-tumor toxicity has remained a major concern. Recent studies suggest that this risk could be obviated by targeting instead combinations of two or more antigens, which are co-expressed by tumor but not normal cells and, as such, are tumor-specific. Moreover, the expression of a shared tumor antigen along with the lack of a second antigen that is expressed by normal tissues can also be exploited for precise recognition. Additional cues, antigenic or non-antigenic ones, which characterize the tumor microenvironment, could be harnessed to further increase precision. This review focuses on attempts to define the targetable signatures of tumors and assesses different strategies employing advanced synthetic biology for translating such information into safer modes of immunotherapy, implementing the principles of Boolean logic gates.
format	article
author	Mohammed Azharuddin Savanur Mohammed Azharuddin Savanur Hadas Weinstein-Marom Hadas Weinstein-Marom Gideon Gross Gideon Gross
author_facet	Mohammed Azharuddin Savanur Mohammed Azharuddin Savanur Hadas Weinstein-Marom Hadas Weinstein-Marom Gideon Gross Gideon Gross
author_sort	Mohammed Azharuddin Savanur
title	Implementing Logic Gates for Safer Immunotherapy of Cancer
title_short	Implementing Logic Gates for Safer Immunotherapy of Cancer
title_full	Implementing Logic Gates for Safer Immunotherapy of Cancer
title_fullStr	Implementing Logic Gates for Safer Immunotherapy of Cancer
title_full_unstemmed	Implementing Logic Gates for Safer Immunotherapy of Cancer
title_sort	implementing logic gates for safer immunotherapy of cancer
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/23442c29f58341b58f7775efe91e8b45
work_keys_str_mv	AT mohammedazharuddinsavanur implementinglogicgatesforsaferimmunotherapyofcancer AT mohammedazharuddinsavanur implementinglogicgatesforsaferimmunotherapyofcancer AT hadasweinsteinmarom implementinglogicgatesforsaferimmunotherapyofcancer AT hadasweinsteinmarom implementinglogicgatesforsaferimmunotherapyofcancer AT gideongross implementinglogicgatesforsaferimmunotherapyofcancer AT gideongross implementinglogicgatesforsaferimmunotherapyofcancer
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Implementing Logic Gates for Safer Immunotherapy of Cancer

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