Cytokines in Cell Therapy
Detecting IFN-gamma in Cytokine-Release Syndrome
to assess the toxicity of your CAR T therapeutic.
14.10.24
Cytokine Release Syndrome (CRS), also known as the “Cytokine
Storm”, is a systemic inflammatory response characterized at the
cellular level by the rapid release of excessive concentrations
of cytokines . Patient symptoms range from mild fever to
hypotension, multiorgan system failure, neurotoxicity and death.
CRS is caused by a variety of events, including viral infection,
antibody-based immunotherapy and cellular immunotherapy.
In antibody-based immunotherapies, the incidence of CRS is
relatively low, however, onset can occur within days and up to
weeks of infusion in cellular immunotherapy. Evidence suggests
that the risk and severity of CRS is influenced by the type of
therapy, disease burden and patient characteristics, such as age.
With respect to the latter, there is a higher incidence of CRS in
pediatric patients. Other correlates include the “first dose effect”,
i.e. the initial infusion stimulates a more robust response than
subsequent infusions.
T cell expansion with increased Interferon Gamma (IFN-γ) release.
Note that increased IFN-γ is also an early and prominent
element of CRS. IFN-γ, along with IL-6, IL-10 and TNF-alpha are the
core cytokines involved in CRS . IFN-γ activates macrophages
which secrete excessive amounts of other cytokines such as
IL-6, TNFα and IL-10. Lastly, it is important to keep in mind that
IFN-γ is pleiotropic and has both harmful and beneficial effects.
Although IFN-γ has a harmful role in CRS, it also been correlated
with antiproliferative, proapoptotic and antitumor activities in the
context of cancer .
We previously described the new 3rd generation R&D Systems®
IFN-γ Quantikine® ELISA kit. Learn more about that assay here.
Here, we describe the R&D Systems® Human IFN-γ Quantikine®
High Sensitivity (HS) ELISA Kit, which has been designed with
increased sensitivity for quantitation in serum and plasma. The
minimal detectable dose (MDD) of this immunoassay is 0.173
pg/mL. Such sensitivity is particularly useful when assessing
baseline IFN-γ secretion which has been reported to range from
0 to 20 pg/mL in healthy individuals .
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