Controlling Cytokine Release Syndrome to Harness the Full Potential of CAR-Based Cellular Therapy. Front Oncol 2019;9:1529
Date
02/23/2020Pubmed ID
32076597Pubmed Central ID
PMC7006459DOI
10.3389/fonc.2019.01529Scopus ID
2-s2.0-85079671509 (requires institutional sign-in at Scopus site) 22 CitationsAbstract
Chimeric Antigen Receptor (CAR)-based therapies offer a promising, targeted approach to effectively treat relapsed or refractory B cell malignancies. However, the treatment-related toxicity defined as cytokine-release syndrome (CRS) often develops in patients, and if uncontrolled, can be fatal. Grading systems have now been developed to further characterize and objectify clinical findings in order to provide algorithm-based guidance on CRS-related treatment decisions. The pharmacological treatments associated with these algorithms suppress inflammation through a variety of mechanisms and are paramount to improving the safety profile of CAR-based therapies. However, fatalities are still occurring, and there are downsides to these treatments, including the possibility of disrupting CAR-T cell persistence. This review article will describe the clinical presentation and current management of CRS, and through our now deeper understanding of downstream signaling pathways, will provide a molecular framework to formulate new hypotheses regarding clinical applications to contain proinflammatory cytokines responsible for CRS.
Author List
Thakar MS, Kearl TJ, Malarkannan SAuthors
Tyce J. Kearl MD, PhD Assistant Professor in the Medicine department at Medical College of WisconsinSubramaniam Malarkannan PhD Professor in the Medicine department at Medical College of Wisconsin
