New research from the Fred Hutchinson Cancer Research Center focuses on designing CARs with improved antigen sensitivity and in vivo function.
In a new study published in Science Signaling, researchers compared antigen-induced pathway signaling in human T-cells expressing a current CAR construct to cells with endogenous T-cell receptors (TCRs), in order to design CAR-T cells with improved antigen sensitivity. They found that key T-cell signaling proteins, including CD3δ, CD3ε, and CD3γ, and TCR adaptor protein LAT, were either not phosphorylated or weakly phosphorylated by CAR stimulation.
By using this information to create modified CARs that better engage signaling proteins, the team created two new CAR designs with superior antigen reactivity in vitro when tested in xenograft mouse models of blood and breast cancer.
“Our study provides important insights on how to design next generation CAR-T cells that could provide lasting remissions from cancer,” said first author Alex Salter in a statement.