Development of molecular and pharmacological switches for chimeric antigen receptor T cells

The use of chimeric antigen receptor (CAR) T cell technology as a therapeutic strategy for the treatment blood-born human cancers has delivered outstanding clinical efficacy. However, this treatment modality can also be associated with serious adverse events in the form of cytokine release syndrome....

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Bibliographic Details
Published in:Experimental hematology & oncology 2019-11, Vol.8 (1), p.27-27, Article 27
Main Authors: Wu, Bill X, Song, No-Joon, Riesenberg, Brian P, Li, Zihai
Format: Article
Language:English
Subjects:
Antigens
Axicabtagene ciloleucel
Cancer
Cetuximab
Cytokines
Dasatinib
Health aspects
Phenols (Class of compounds)
T cells
Technology
Tisagenlecleucel
Toxicity
Tyrosine
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Summary:The use of chimeric antigen receptor (CAR) T cell technology as a therapeutic strategy for the treatment blood-born human cancers has delivered outstanding clinical efficacy. However, this treatment modality can also be associated with serious adverse events in the form of cytokine release syndrome. While several avenues are being pursued to limit the off-target effects, it is critically important that any intervention strategy has minimal consequences on long term efficacy. A recent study published in Science Translational Medicine by Dr. Hudecek's group proved that dasatinib, a tyrosine kinase inhibitor, can serve as an on/off switch for CD19-CAR-T cells in preclinical models by limiting toxicities while maintaining therapeutic efficacy. In this editorial, we discuss the recent strategies for generating safer CAR-T cells, and also important questions surrounding the use of dasatinib for emergency intervention of CAR-T cell mediated cytokine release syndrome.
ISSN:2162-3619
2162-3619
DOI:10.1186/s40164-019-0151-z