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Engineering CAR-expressing natural killer cells with cytokine signaling and synthetic switch for an off-the-shelf cell-based cancer immunotherapy

Published online by Cambridge University Press:  27 March 2019

Yun Qu ,
Elizabeth Siegler ,
Chumeng Cheng ,
Jiangyue Liu ,
Gunce Cinay ,
Neelesh Bagrodia  and
Pin Wang Open the ORCID record for Pin Wang [Opens in a new window]
Yun Qu
Affiliation:
Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA 90089, USA
Elizabeth Siegler
Affiliation:
Department of Biomedical Engineering, University of Southern California, Los Angeles, CA 90089, USA
Chumeng Cheng
Affiliation:
Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA 90089, USA
Jiangyue Liu
Affiliation:
Department of Molecular Microbiology & Immunology, University of Southern California, Los Angeles, CA 90089, USA
Gunce Cinay
Affiliation:
Department of Biomedical Engineering, University of Southern California, Los Angeles, CA 90089, USA
Neelesh Bagrodia
Affiliation:
Department of Biomedical Engineering, University of Southern California, Los Angeles, CA 90089, USA
Pin Wang*
Affiliation:
Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA 90089, USA Department of Biomedical Engineering, University of Southern California, Los Angeles, CA 90089, USA
*
Address all correspondence to Pin Wang at pinwang@usc.edu
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Abstract

Immune cells can be genetically engineered with a synthetic chimeric antigen receptor (CAR) to eliminate cancer cells, but clinical efficacy in solid tumors has been disappointing due in part to the immunosuppressive tumor microenvironment (TME). Additionally, the cost and logistical issues of personalized medicine necessitate the creation of an off-the-shelf CAR therapy. Synthetic biology tools were implemented in addressing these problems: an anti-mesothelin CAR, membrane-bound IL-15/IL-15Rα complex, and inducible caspase 9 “kill switch” were expressed in natural killer cells for tumor-targeting capabilities, immunostimulatory effects, and safety in treating a preclinical model of ovarian cancer with a renewable, allogenic cell therapy.

Type
Synthetic Biology Research Letter
Information
MRS Communications , Volume 9 , Issue 2 , June 2019 , pp. 433 - 440
Copyright
Copyright © Materials Research Society 2019 

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Footnotes

*

Authors contributed equally to this work.

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