JAML transmembrane and co-signaling domains for chimeric antigen receptors

Abstract

The present disclosure relates to the field of cell therapy, and more specifically, to chimeric antigen receptor (CAR) cell therapy. In one embodiment, the disclosure provides CAR-T constructs comprising transmembrane and / or co-stimulatory cytoplasmic domains of JAML. In one embodiment, the disclosure provides CAR-T cells that co-express two CAR-T constructs, or a bicistronic construct, one of which comprises a JAML transmembrane and / or co-stimulatory domain. In one embodiment, the disclosure provides CAR-T cells that co-express a CAR-T construct and a full length JAML construct. In one embodiment, the disclosure provides a chimeric construct comprising a TGFbeta- receptor with an intracellular JAML domain, or a fragment thereof, and cells expressing the same. In one embodiment, the disclosure provides methods of treating cancer and autoimmune disorders with the constructs and cells of the disclosure.

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