USE OF CART19 TO DEPLETE NORMAL B CELLS TO INDUCE TOLERANCE

• US 20150290244A1
• Filed: 07/12/2013
• Published: 10/15/2015
• Est. Priority Date: 07/13/2012
• Status: Abandoned Application

• Current Assignee: LG Chem Limited (LG Corporation), Trustees Of The University Of Pennsylvania (University of Pennsylvania)
• Original Assignee: Trustees Of The University Of Pennsylvania (University of Pennsylvania)
• Inventors: June, Carl H., Levine, Bruce L., Kalos, Michael D.
• Application Number:
  US14/413,100
• Publication Number:
  US 20150290244A1
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2035/122 for inducing tolerance or supression of immune responses
• CPC Class Codes: A61K 2239/38 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 2239/48 Blood cells, e.g. leukemia or lymphoma
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61K 35/17 Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes when activated by a specific antigen A61K39/00
• CPC Class Codes: A61K 38/177 Receptors; Cell surface antigens; Cell surface determinants
• CPC Class Codes: A61K 39/4611 T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
• CPC Class Codes: A61K 39/4631 Chimeric Antigen Receptors [CAR]
• CPC Class Codes: A61K 39/464412 CD19 or B4
• CPC Class Codes: A61K 48/005 characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection

Abstract

The present invention provides compositions and methods for inducing tolerance in a human. The invention includes administering a genetically modified T cell expressing a CAR wherein the CAR comprises an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain.

Claims

1. A method of depleting B cells in a subject, the method comprising administering to a subject an effective amount of a cell genetically modified to express a CAR wherein the CAR comprises an antigen binding domain, a costimulatory signaling region, and a CD3 zeta signaling domain, wherein the antigen binding domain targets a B cell surface marker, thereby depleting B cells in the subject.

2. A method of promoting tolerance in a subject, the method comprising administering to a subject an effective amount of a cell genetically modified to express a CAR wherein the CAR comprises an antigen binding domain, a costimulatory signaling region, and a CD3 zeta signaling domain, wherein the antigen binding domain targets a B cell surface marker, thereby promoting tolerance in the subject.

3. The method of claim 2, wherein the tolerance is transplant tolerance to a transplanted tissue.

4. The method of claim 2, wherein the genetically modified cell depletes B cells.

5. The method of claim 2, wherein the genetically modified cell is administered at the same time as the transplanted tissue.

6. The method of claim 2, wherein the genetically modified cell is administered before the administration of the transplanted tissue.

7. The method of claim 2, wherein the genetically modified cell is administered after the administration of the transplanted tissue.

8. A method for treating graft versus host disease (GVHD), the method comprising administering a cell genetically modified to express a CAR to a subject in need thereof, wherein the CAR comprises an antigen binding domain, a costimulatory signaling region, and a CD3 zeta signaling domain, wherein the antigen binding domain targets a B cell surface marker, thereby treating GVHD in the subject.

9. The method of claim 8, wherein the genetically modified cell depletes B cells.

10. The method of claim 8, wherein the genetically modified cell is administered at the same time as a transplanted tissue.

11. The method of claim 8, wherein the genetically modified cell is administered before the administration of the transplanted tissue.

12. The method of claim 8, wherein the genetically modified cell is administered after the administration of the transplanted tissue.