Recombinant CAR cells may result in a rapid and excessive release of cytokines, which can lead to cytokine release syndrome (CRS), sometimes referred to as cytokine storms. Cytokine storms can cause significant and potentially life-threatening toxicities, and patients feel very uncomfortable. Macromolecular therapeutics (e.g., vaccines, therapeutic mAbs, and other biological agents) have the same risks.
Since CRS is a direct result of super-physiological levels of inflammatory cytokines, circulating cytokine levels can be served as biomarkers for the diagnosis and potential quantification of the severity of the syndrome. However, currently, there are several issues that limit the effectiveness of this approach, so real-time analysis of cytokines does not significantly affect the management of CRS.
Therefore, here, Creative Biolabs evaluates the CRS based on the revised severity rating system and tries to help you predict new effective biomarkers for CRS management.
FDA and other regulatory agencies have recently published guidelines for assessing immunogenicity, including treatments for evaluating cytokine release syndrome. Transgenic mice of Creative Biolabs mimic human cytokine responses and disorders by injecting CAR-T cells, making them ideal for assessing and alleviating adverse immune-related responses associated with treatments that affect their safety and efficacy.
CRS has typical clinical manifestations, usually characterized by hyperthermia, hypotension, hypoxia, and respiratory distress. Organ dysfunction can occur, such as liver transaminases and renal insufficiency. The National Cancer Institute Common Terminology Standard for Adverse Events (CTCAE v4.0) contains a CRS grading system associated with antibodies and cell therapy, defining CRS as mild, moderate, severe, and life-threatening CRS. We refer to this CRS rating system for evaluation.
Currently, the main cells and cytokines that mediate CRS include IL-1, IL-6, TNF, IFNγ, macrophages and monocytes. One of the key cytokine mediators is IL-6. The IL-6 receptor antibody is currently the first line to treat and manage CRS.
Our scientists are committed to working with laboratory research teams to discover more biomarkers to predict CRS.
For more details, please feel free to contact us for project quotations and more detailed information.
For Research Use Only | Not For Clinical Use
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