University of Würzburg myeloma researchers have identified that a tyrosine kinase inhibitor called dasatinib can act as an on/off switch for CAR T cells without affecting the T cells’ viability.
Significant CAR T cell therapy is in development for multiple myeloma in over a dozen clinical trials. The most common target in development for multiple myeloma patients is BCMA, but additional targets such as CS1 and others are being tested as the new immunotherapy platform matures.
CAR T cells are single-shot “living drugs” that require technologies to enable physicians (and patients) to maintain control over the infused cell product. CAR T cells can persist in patients for several years and can continue to expand over time. One potential side effect of CAR T therapy is called cytokine release syndrome (CRS) and can cause severe toxicity and even death in a small number of patients.
Dasatinib can turn off CD8+ and CD4+ CAR T cells and this off-switch can be sustained for several days without impacting the usability of the CAR T cells. Dasatinib stops cytokine production and the expansion of CAR T cells. The dose can be modified to achieve partial or full inhibition and once dasatinib is stopped, the CAR T cells can turn back on and continue their anti-tumor work. The on/off switching can happen in real time.
In mouse models, the researchers showed that a short treatment course of dasatinib, when administered early after CAR T cell infusion, protects a proportion of mice from otherwise fatal CRS.
Dasatinib is an inhibitor currently being used in chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL).
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