Engineering cytokine receptors to control cellular functions

Kawahara, Masahiro; Ueda, Hiroshi; Nagamune, Teruyuki

doi:10.1016/j.bej.2009.09.010

Cited by 22 publications

(19 citation statements)

References 175 publications

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“…In particular, these receptors mediate chemical sensing, cell-to-cell communication and antigen recognition. Chimeric cytokine receptors and chimeric antigen receptors (CAR) are both a novel application of synthetic signaling pathway engineering and a potential treatment for certain types of cancer (Geiger and Jyothi 2001;Kawahara et al 2010). CARs consist generally of three parts: an exterior sensing domain, a single transmembrane domain, and an intracellular signaling domain.…”

Section: Mammalian Cellsmentioning

confidence: 99%

Synthetic biology of cell signaling

Hansen

Benenson

2015

Nat Comput

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Synthetic biology often takes cues from complex natural networks and pathways to create novel biological systems. The design modalities used in synthetic systems generally follow the different classes of gene regulation in cells such as transcriptional, post-transcriptional and post-translational regulation. The latter class is most prominent in cell signaling pathways that operate via multitude of protein-protein interactions. Engineering signaling pathways is a relatively unexplored area. This review discussed the work toward signaling pathway engineering in diverse biological contexts including bacteria, yeast, vertebrate, and plant cells. While creating synthetic signaling cascades is perhaps one of the most challenging tasks in synthetic biology, potential implications can be far-reaching and include new tools for programming cells and tissues, artificial developmental processes, and therapeutic tools.

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Section: Mammalian Cellsmentioning

confidence: 99%

Synthetic biology of cell signaling

Hansen

Benenson

2015

Nat Comput

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“…For example, heterodimerization of the β chain and common γ chain of the IL-2 receptor can be mediated by other modalities if the ligand-binding domains are removed (75). Several groups have shown that the extracellular domains of the two chains can be replaced and alternative proteins can be used to drive heterodimerization and signaling through the receptor (76).…”

Section: Synthetic Biology Tool Kit: Genetic Components For Programmimentioning

confidence: 99%

Synthetic Immunology: Hacking Immune Cells to Expand Their Therapeutic Capabilities

Roybal

Lim

2017

Annu. Rev. Immunol.

111

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The ability of immune cells to survey tissues and sense pathologic insults and deviations makes them a unique platform for interfacing with the body and disease. With the rapid advancement of synthetic biology, we can now engineer and equip immune cells with new sensors and controllable therapeutic response programs to sense and treat diseases that our natural immune system cannot normally handle. Here we review the current state of engineered immune cell therapeutics and their unique capabilities compared to small molecules and biologics. We then discuss how engineered immune cells are being designed to combat cancer, focusing on how new synthetic biology tools are providing potential ways to overcome the major roadblocks for treatment. Finally, we give a long-term vision for the use of synthetic biology to engineer immune cells as a general sensor-response platform to precisely detect disease, to remodel disease microenvironments, and to treat a potentially wide range of challenging diseases.

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“…To this end, we developed a platform technology using chimeric receptors in which the ligand‐recognition domain of receptors is replaced by single‐chain Fv (scFv). Such engineered receptors, which we term “signalobodies,” can recognize a specific antigen with the scFv region, and transduce signals derived from the receptors . To date, we have created signalobodies based on epidermal growth factor receptor (EGFR), stem cell factor receptor (SCFR; c‐kit), macrophage colony‐stimulating factor receptor (M‐CSFR; c‐fms), and insulin receptor (IR) .…”

Section: Introductionmentioning

confidence: 99%

Cell‐Surface Expression Levels Are Important for Fine‐Tuning the Performance of Receptor Tyrosine Kinase‐Based Signalobodies

Nakabayashi

Kawahara

Nagamune

2017

Biotechnology Journal

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As receptor tyrosine kinases (RTKs) play important roles in cell-fate control of various cell types, engineered RTKs that could respond to inexpensive ligands might drastically reduce the cost of producing desired cells for various applications in regenerative medicine. We developed several engineered RTKs named "signalobodies" in which the ligand-recognition domain of RTKs is replaced by single-chain Fv for enabling recognition of a specific antigen. However, the remaining concern was the dysregulation of antigen-dependent on/off signaling of the signalobodies. This study aims at fine-tuning the performance of the signalobodies based on three RTKs (fibroblast growth factor receptor 1, insulin receptor, and c-fms). To this end, the cell-surface expression levels of the RTK-based signalobodies were altered by locating their genes either upstream or downstream of the internal ribosomal entry site, and by inserting 1 to 3 alanine residue(s) at the intracellular juxtamembrane region. As a result, while the signaling response was different among the three signalobodies, the antigen-dependent on/off regulation became tighter when the cell-surface expression levels of the signalobodies were lowered. Therefore, we successfully developed a method to diminish the leaky signaling of RTK-based signalobodies, which will be important for establishing the signalobody-based platform technology that can produce cells of interest for regenerative medicine.

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Engineering cytokine receptors to control cellular functions

Cited by 22 publications

References 175 publications

Synthetic biology of cell signaling

Synthetic biology of cell signaling

Synthetic Immunology: Hacking Immune Cells to Expand Their Therapeutic Capabilities

Cell‐Surface Expression Levels Are Important for Fine‐Tuning the Performance of Receptor Tyrosine Kinase‐Based Signalobodies

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