Chimeric antigen receptors (CARs) have been developed and used as a therapeutic for cancers of the blood and bone marrow. These CARs have defined antigens that can be targeted by engineered effector T cells. CARs run the risk of severe toxicity and can trigger cytokine release syndrome (CRS), a dangerous systemic inflammatory syndrome characterized by fever and multiple organ dysfunction, limiting their therapeutic use.
Description
The discovery that a cell-surface protein Tim-3 has the ability to co-stimulate T cell activation has enabled the construction of an anti-CD20 CAR in which the TCR zeta stimulatory domain was paired with the cytoplasmic domain of Tim-3. This construct displays comparable in vitro CAR activity against CD20-expressing leukemia cells to an analogue CAR containing the cytoplasmic domain of CD28 and formed comparable CAR immune synapses. Researchers hope that this novel method of incorporating the intracellular signaling domain of Tim-3 may lead to more sustained in vivo activation of of T cells expressing this CAR and reduced in vivo toxicity.
Applications
· Treating cancers of the blood and bone marrow
Advantages
· May extend the duration of in vivo activation of T cells expressing this CAR
· May reduce in vivo toxicity and risk of cytokine release syndrome
Invention Readiness
In vitro data
IP Status
https://patents.google.com/patent/US20240122980A1
