Car-t cells and autoimmune diseases
AssigneeThe Regents of the University of California
InventorsJEFFREY A. BLUESTONE, CAROLINE RAFFIN
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Abstract
Chimeric antigen receptor (CAR)-expressing Tregs specifically target an antigen present in the joint of RA patients to induce a localized and effective immunosuppressive response.
Claims51
A chimeric antigen receptor (CAR) comprising an antigen specific binding domain, a hinge domain, a transmembrane domain, co-stimulatory domain, and a CD3ζ signaling domain, wherein the antigen specific binding domain specifically binds to antigens comprising vimentin polypeptides or peptides thereof.
An isolated T cell that is modified to express:
- a chimeric antigen receptor (CAR) comprising an antigen binding domain linked to at least one co-stimulatory domain and a CD3ζ signaling domain, wherein the antigen binding domain comprises a single chain variable fragment (scFv) which specifically binds to citrullinated-vimentin (CV).
A method of treating a subject diagnosed with rheumatoid arthritis, comprising:
- isolating T lymphocytes from a biological sample obtained from the subject;
- separating CD4+ T regulatory Cells (Treg) from conventional T cells (Tconv), wherein the Treg cells are CD4+CD25+CD127− and the Tconv are CD4+CD25−CD127+;
- transducing the Treg cells with an expression vector encoding a chimeric antigen receptor (CAR) which specifically binds to a citrullinated-vimentin (CV) antigen;
- expanding the transduced Treg with anti-CD3/CD28 beads at least once ex vivo to obtain expanded Treg cells specific for the CV antigen;
- and
- reinfusing the Treg into the subject, thereby treating the subject.
A chimeric antigen receptor (CAR) comprising an antigen binding domain, a hinge domain, a transmembrane domain, co-stimulatory domain, and a CD3ζ signaling domain, wherein the antigen specific domain comprises an antibody or antibody fragment.
Dependencies are inferred from the claim text.