Citrullinated antigen-specific chimeric antigen receptors for targeting regulatory t cells to treat hidradenitis suppurativa
AssigneeSonoma Biotherapeutics, Inc.
InventorsLeonard DRAGONE, Joshua BEILKE
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Abstract
Disclosed herein are chimeric antigen receptors (CARs) comprising an antigen binding site that recognizes citrullinated polypeptides. Citrullinated polypeptides, such as citrullinated vimentin, are expressed in the skin lesions of subjects with hidradenitis suppurativa. Further disclosed are T cells, and in particular, Treg cells that express these CARs. Administration of these CAR-T cells is useful in the treatment of hidradenitis suppurativa.
Claims34
A method of treating a subject suffering from hidradenitis suppurativa, comprising administering to the subject an effective amount of a pharmaceutical composition comprising a plurality of modified regulatory T (Treg) cells and a pharmaceutically acceptable excipient, wherein
- the modified Treg cells express a chimeric antigen receptor (CAR) comprising an antigen-binding domain, a hinge domain, a transmembrane domain, one or more co-stimulatory domains, and an intracellular signaling domain,
- the antigen binding domain specifically binds to one or more different citrullinated proteins or citrullinated fragments thereof, and
- the modified Treg cells are CD4+, CD25+ and CD127lo.
A method of treating a subject suffering from hidradenitis suppurativa, the method comprising:
- (a) isolating T cells from a biological sample obtained from the subject;
- (b) enriching the T cells for T regulatory cells (Treg);
- (c) transfecting the enriched Treg cells with an expression vector encoding a chimeric antigen receptor (CAR) comprising an antigen-binding domain, a hinge domain, a transmembrane domain, one or more co-stimulatory domains, and an intracellular signaling domain to produce modified Treg cells expressing the CAR, wherein
- the antigen binding domain specifically binds to one or more different citrullinated proteins or citrullinated fragments thereof, and
- the modified Treg cells are CD4+, CD25+ and CD127lo;
- (d) expanding the modified Treg cells;
- and
- (e) administering the modified Treg cells to the subject.
Use of a plurality of modified regulatory T (Treg) cells in the manufacture of a medicament for treating hidradenitis suppurativa in a subject, wherein
- the modified Treg cells express a chimeric antigen receptor (CAR) comprising an antigen-binding domain, a hinge domain, a transmembrane domain, one or more co-stimulatory domains, and an intracellular signaling domain,
- the antigen binding domain specifically binds to one or more different citrullinated proteins or citrullinated fragments thereof, and
- the modified Treg cells are CD4+, CD25+ and CD127lo.
A plurality of modified regulatory T (Treg) cells for use in a method of treating hidradenitis suppurativa in a subject, the method comprising administering to the subject the plurality of modified regulatory T (Treg) cells, wherein
- the modified Treg cells express a chimeric antigen receptor (CAR) comprising an antigen-binding domain, a hinge domain, a transmembrane domain, one or more co-stimulatory domains, and an intracellular signaling domain,
- the antigen binding domain specifically binds to one or more different citrullinated proteins or citrullinated fragments thereof, and
- the modified Treg cells are CD4+, CD25+ and CD127lo.
Dependencies are inferred from the claim text.