Ibrutinib Inhibits Human CD4 T Cell Proliferation
Abstract
Ibrutinib, is an orally active agent, which works by covalent irreversible binding to the kinase domain of Bruton’s Tyrosine Kinase (BTK). The drug is of central importance in B cell receptor signaling and is currently used to treat B cells cancers like Chronic Lymphocytic Leukemia and B Cell Lymphoma. In addition to BTK inhibition, it has been hypothesized that Ibrutinib is a target of Interleukin-2 Inducible Kinase (ITK), which is an active agent in T cell malignancies survival and proliferation. The purpose of this experiment was to determine the effect of Ibrutinib on human T cells. Peripheral blood mononuclear cells (PBMCs) were isolated, activated, and analyzed using Carboxyfluorescein succinimidyl ester (CFSE) proliferation assay and Fluorescence-activated cell sorting (FACS) analysis in presence and absence of the drug, Ibrutinib, at different concentrations. Our results indicate that Ibrutinib inhibits Tcell proliferation, in particular, CD4 T cells. The inhibition was noted as being dose dependent. In overall, our findings demonstrate the significance of Ibrutinib as an Interleukin-2 Inducible Kinase inhibitor and could lead to potential new therapeutic uses for the treatment of T cell malignancies. Moreover, Ibrutinib could aid in the treatment of B cell malignancies by two different mechanisms, BTK and ITK inhibition.
Faculty Sponsors
Dr. Aarti Raja, Dr. Qing Ma, Dr. Dan Li
Project Type
Event
Location
Alvin Shermany Library
Start Date
4-5-2019 1:00 PM
End Date
4-5-2019 5:00 PM
Ibrutinib Inhibits Human CD4 T Cell Proliferation
Alvin Shermany Library
Ibrutinib, is an orally active agent, which works by covalent irreversible binding to the kinase domain of Bruton’s Tyrosine Kinase (BTK). The drug is of central importance in B cell receptor signaling and is currently used to treat B cells cancers like Chronic Lymphocytic Leukemia and B Cell Lymphoma. In addition to BTK inhibition, it has been hypothesized that Ibrutinib is a target of Interleukin-2 Inducible Kinase (ITK), which is an active agent in T cell malignancies survival and proliferation. The purpose of this experiment was to determine the effect of Ibrutinib on human T cells. Peripheral blood mononuclear cells (PBMCs) were isolated, activated, and analyzed using Carboxyfluorescein succinimidyl ester (CFSE) proliferation assay and Fluorescence-activated cell sorting (FACS) analysis in presence and absence of the drug, Ibrutinib, at different concentrations. Our results indicate that Ibrutinib inhibits Tcell proliferation, in particular, CD4 T cells. The inhibition was noted as being dose dependent. In overall, our findings demonstrate the significance of Ibrutinib as an Interleukin-2 Inducible Kinase inhibitor and could lead to potential new therapeutic uses for the treatment of T cell malignancies. Moreover, Ibrutinib could aid in the treatment of B cell malignancies by two different mechanisms, BTK and ITK inhibition.
