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In-vitro tests in human T-cells demonstrated that CD40 signaling domain is a potent costimulatory element for both 2nd and 3rd generation CARs.
About
The costimulatory domains incorporated into second and third generation chimeric antigen receptors (CARs) strongly influence CAR-T cell function.
We explored 2nd and 3rd generation CARs harboring the signaling domain of the CD40 receptor as a new costimulatory element in comparison with similar CARs carrying the 4-1BB domain. In CARs of both generations, CD40 was more potent than 4-1BB in triggering the NF-kB signaling pathway. In human T cells from two donors CD40 was comparable to 4-1BB in upregulating costimulatory and activation markers, inducing proinflammatory cytokines secretion and mediating target cell killing. Interestingly, differences in the response pattern of T cells from the two donors with respect to CD40 and 4-1BB were evident.
We conclude that in human T cells the CD40 signaling domain is a potent costimulatory element in both 2nd and 3rd generation CARs.
Key Benefits
The invention is applicable as a general CAR platform for redirecting effector T cells (and NK cells) in cancer immunotherapy or regulatory T cells (Tregs) in autoimmune and inflammatory diseases.
Applications
cancer immunotherapy, autoimmune and inflammatory diseases