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

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 perso...

Full description

Saved in:
Bibliographic Details
Published inMRS communications Vol. 9; no. 2; pp. 433 - 440
Main Authors Qu, Yun, Siegler, Elizabeth, Cheng, Chumeng, Liu, Jiangyue, Cinay, Gunce, Bagrodia, Neelesh, Wang, Pin
Format Journal Article
LanguageEnglish
Published New York, USA Cambridge University Press 01.06.2019
Springer International Publishing
Subjects
Antigens
Biomaterials
Cancer
Cancer therapies
Cell growth
Characterization and Evaluation of Materials
Clinical trials
Cytokines
Cytotoxicity
Genetic engineering
Immune system
Immunotherapy
Lymphocytes
Materials Engineering
Materials Science
Nanotechnology
Polymer Sciences
Synthetic biology
Synthetic Biology Research Letter
Therapy
Tumors
United States > US
Online AccessGet full text

Cover

More Information
Summary: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.
ISSN:2159-6859
2159-6867
DOI:10.1557/mrc.2019.31