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Cytokine Release Syndrome and CAR-T cells: Challenges to Cutting-Edge Therapies

Posted on: November 07, 2019

T Cells

Personalized cancer treatments, particularly chimeric antigen receptor (CAR) T cell therapy, have revolutionized the treatment of blood cancers and solid tumors. CAR T cell-based treatments use genetically modified T cells from a patient that are engineered to express a modified T cell receptor, which includes an extracellular binding domain that binds specifically to a patient’s tumor antigen, a transmembrane domain, and an intracellular domains that has multiple costimulatory domains (i.e., CD28, 4-1BB). Patients typically undergo lymphodepletion chemotherapy and are infused with their specific CAR -T cells, which are activated upon encounter with tumor antigen and can proliferate and lyse tumor cells. Although this type of treatment has been shown to be very effective for treating a wide range of tumors, severe side effects can occur, including cytokine release syndrome (CRS). Flow cytometry is a critical tool for understanding CRS and identifying biomarkers that may predict the onset of this complication.

What is CRS?

Upon activation of CAR-T cells in patients, lysis of target tumor cells can occur at such a large scale that massive amounts of inflammatory cytokines are released and manifest as symptoms that resemble sepsis, including fever, fatigue, capillary leakage, tachycardia, and liver and kidney failure. IL-6 appears to be a key mediator of CRS, and inhibition of IL-6 or corticosteroid treatment can manage the severity of this adverse event.

Cytokine-release-1

Flow Cytometry Tools for CRS

Flow cytometry has been instrumental to the development of CAR-T cell therapies and for characterizing CRS. In particular, flow cytometry-based measurements of tumor burdens in bone marrow for blood cancers, as well as quantification of CAR-T cells and inflammatory cytokines in blood during and immediately following treatment, have been critical early indicators for predicting severity of CRS before onset. These tools continue to be improved and refined in order to better predict CRS.

Expertise in flow cytometry is critical to advancing the development of personalized therapeutics like CAR-T cells. Consider working with a flow cytometry contract research organization if you are in the preclinical phase of development or are ready to commence clinical trials.

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