The adoptive transfer of T cells expressing a chimeric antigen receptor (CAR) is an effective therapy for patients with relapsed or refractory CD19+ B cell malignancies, but can cause life-threatening toxicities. Herein we discuss a recent study suggesting that alterations to the design of anti-CD19 CARs can reduce cytokine release and the incidence of treatment-related complications.
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References
Sadelain, M., Riviere, I. & Riddell, S. Therapeutic T cell engineering. Nature 545, 423–431 (2017).
Gauthier, J. & Turtle, C. J. Insights into cytokine release syndrome and neurotoxicity after CD19-specific CAR-T cell therapy. Curr. Res. Transl Med. 66, 50–52 (2018).
Lee, D. W. et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood 124, 188–195 (2014).
Gust, J. et al. Endothelial activation and blood-brain barrier disruption in neurotoxicity after adoptive immunotherapy with CD19 CAR-T cells. Cancer Discov. 7, 1404–1419 (2017).
Neelapu, S. S. et al. Chimeric antigen receptor T cell therapy — assessment and management of toxicities. Nat. Rev. Clin. Oncol. 15, 47–62 (2018).
Hay, K. A. et al. Kinetics and biomarkers of severe cytokine release syndrome after CD19 chimeric antigen receptor-modified T cell therapy. Blood 130, 2295–2306 (2017).
Maloney, D. G. Anti-CD19 CAR T cell therapy for lymphoma — off to the races! Nat. Rev. Clin. Oncol. 16, 279–280 (2019).
Salter, A. I. et al. Phosphoproteomic analysis of chimeric antigen receptor signaling reveals kinetic and quantitative differences that affect cell function. Sci. Signal. 11, eaat6753 (2018).
Feucht, J. et al. Calibration of CAR activation potential directs alternative T cell fates and therapeutic potency. Nat. Med. 545, 423 (2018).
Ying, Z. et al. A safe and potent anti-CD19 CAR T cell therapy. Nat. Med. https://doi.org/10.1038/s41591-019-0421-7 (2019).
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A.I.S. and S.R.R. hold patents related to CAR design that have been licensed to Lyell Immunopharma. A.I.S. is a consultant for and holds equity in Lyell Immunopharma. S.R.R. is a scientific founder of, holds equity in and receives research funding from Juno Therapeutics–Celgene and Lyell Immunopharma.
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Salter, A.I., Riddell, S.R. Tinkering in the garage — tuning CARs for safety. Nat Rev Clin Oncol 16, 530–532 (2019). https://doi.org/10.1038/s41571-019-0240-2
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DOI: https://doi.org/10.1038/s41571-019-0240-2
