Regulatory T cell expressing a chimeric antigen receptor
The present invention provides a regulatory T (Treg) cell expressing an antigen chimeric receptor (CAR) comprising a) at least one antigen binding domain, b) a transmembrane domain, and c) a cytoplasmic signaling domain comprising at least one primary cytoplasmic signaling domain and at least the co-stimulatory signaling domain of CD137, wherein said antigen binding domain specifically binds an antigen that is expressed on the surface of a target cell or a tag of a tagged polypeptide that binds to an antigen expressed on the surface of a target cell or a soluble antigen. Compositions comprising said Treg cells, and methods of enrichment and analysis of activated Tregs that express said CAR are also disclosed.
1. A combination of pharmaceutical compositions comprising
i) a population of human Treg cells expressing a CAR together with a pharmaceutical acceptable carrier, the CAR comprising
a) at least one antigen binding domain,
b) a transmembrane domain,
c) a cytoplasmic signaling domain comprising at least one primary cytoplasmic signaling domain and at least the co-stimulatory signaling domain of CD137, wherein said at least one antigen binding domain specifically binds dextran; and
ii) a dextran molecule that is not conjugated to an antibody or another attachment structure which allows specific targeting of the dextran to cells or tissue matrix surfaces in vivo,
thereby allowing the activation of said Treg cell upon binding of dextran to said at least one antigen binding domain of said CAR.
2. The composition according to claim 1 for treatment of an autoimmune disease, allergy, transplant rejection, graft versus host disease, chronic inflammatory diseases, inflammatory bowel diseases, or a chronic infection by virus, bacteria, or parasite.