A synthetic biology approach to engineering circuits in immune cells.
immunoengineering
immunology
synthetic biology
synthetic circuits
Journal
Immunological reviews
ISSN: 1600-065X
Titre abrégé: Immunol Rev
Pays: England
ID NLM: 7702118
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
received:
23
05
2023
accepted:
08
06
2023
medline:
23
11
2023
pubmed:
19
7
2023
entrez:
19
7
2023
Statut:
ppublish
Résumé
A synthetic circuit in a biological system involves the designed assembly of genetic elements, biomolecules, or cells to create a defined function. These circuits are central in synthetic biology, enabling the reprogramming of cellular behavior and the engineering of cells with customized responses. In cancer therapeutics, engineering T cells with circuits have the potential to overcome the challenges of current approaches, for example, by allowing specific recognition and killing of cancer cells. Recent advances also facilitate engineering integrated circuits for the controlled release of therapeutic molecules at specified locations, for example, in a solid tumor. In this review, we discuss recent strategies and applications of synthetic receptor circuits aimed at enhancing immune cell functions for cancer immunotherapy. We begin by introducing the concept of circuits in networks at the molecular and cellular scales and provide an analysis of the development and implementation of several synthetic circuits in T cells that have the goal to overcome current challenges in cancer immunotherapy. These include specific targeting of cancer cells, increased T-cell proliferation, and persistence in the tumor microenvironment. By harnessing the power of synthetic biology, and the characteristics of certain circuit architectures, it is now possible to engineer a new generation of immune cells that recognize cancer cells, while minimizing off-target toxicities. We specifically discuss T-cell circuits for antigen density sensing. These circuits allow targeting of solid tumors that share antigens with normal tissues. Additionally, we explore designs for synthetic circuits that could control T-cell differentiation or T-cell fate as well as the concept of synthetic multicellular circuits that leverage cellular communication and division of labor to achieve improved therapeutic efficacy. As our understanding of cell biology expands and novel tools for genome, protein, and cell engineering are developed, we anticipate further innovative approaches to emerge in the design and engineering of circuits in immune cells.
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
120-137Subventions
Organisme : Burroughs Wellcome Fund
Organisme : Chan-Zuckerberg Biohub - San Francisco
Organisme : The V Foundation
Informations de copyright
© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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