Implementing Logic Gates for Safer Immunotherapy of Cancer.

Autor:	Savanur MA; Laboratory of Immunology, MIGAL - Galilee Research Institute, Kiryat Shmona, Israel.; Department of Biotechnology, Tel-Hai College, Upper Galilee, Israel., Weinstein-Marom H; Laboratory of Immunology, MIGAL - Galilee Research Institute, Kiryat Shmona, Israel.; Department of Biotechnology, Tel-Hai College, Upper Galilee, Israel., Gross G; Laboratory of Immunology, MIGAL - Galilee Research Institute, Kiryat Shmona, Israel.; Department of Biotechnology, Tel-Hai College, Upper Galilee, Israel.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2021 Nov 04; Vol. 12, pp. 780399. Date of Electronic Publication: 2021 Nov 04 (Print Publication: 2021).
DOI:	10.3389/fimmu.2021.780399
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Savanur, Weinstein-Marom and Gross.)
Databáze:	MEDLINE
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