SWITCH COSTIMULATORY RECEPTORS

• US 20140219975A1
• Filed: 07/27/2012
• Published: 08/07/2014
• Est. Priority Date: 07/29/2011
• Status: Active Grant

• Current Assignee: Trustees Of The University Of Pennsylvania (University of Pennsylvania)
• Original Assignee: Trustees Of The University Of Pennsylvania (University of Pennsylvania)
• Inventors: June, Carl H., Zhao, Yangbing
• Granted Patent: US 10,981,969 B2
• Time in Patent Office: Days
• US Class Current: 424/93.21
• CPC Class Codes: A61K 2239/17 Hinge-spacer domain
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 38/1774 Immunoglobulin superfamily (e.g. CD2, CD4, CD8, ICAM molecules, B7 molecules, Fc-receptors, MHC-molecules)
• 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 39/464411 Immunoglobulin superfamily
• 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 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C07K 14/70503 Immunoglobulin superfamily
• CPC Class Codes: C07K 14/7051 T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C07K 14/70521 CD28, CD152
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 2319/03 containing a transmembrane segment

Abstract

The present invention relates generally to a fusion protein that when displayed on a cell can convert a negative signal into a positive signal in the cell. The fusion protein is a chimeric protein in that the protein comprises at least two domains, wherein the first domain is a polypeptide that is associated with a negative signal and the second domain is a polypeptide that is associated with a positive signal. Thus, the invention encompasses switch receptors that are able to switch negative signals to positive signals for enhancement of an immune response.

Claims

1. A fusion protein comprising a first domain and a second domain, wherein said first domain is a polypeptide that is associated with a negative signal and said second domain is a polypeptide that is associated with a positive signal.

2. The fusion protein of claim 1, wherein said first domain is at least a portion of the extracellular domain of the polypeptide that is associated with a negative signal and said second domain is at least a portion of the intracellular domain of the polypeptide that is associated with a positive signal.

3. The fusion protein of claim 1, further comprising a transmembrane domain.

4. The fusion protein of claim 3, wherein said transmembrane domain is the transmembrane domain of the polypeptide that is associated with a negative signal or the transmembrane domain of the polypeptide that is associated with a positive signal.

5. The fusion protein of claim 1, wherein said polypeptide that is associated with a negative signal is selected from the group consisting of CTLA4, PD-1 and BTLA.

6. The fusion protein of claim 1, wherein said polypeptide that is associated with a positive signal is selected from the group consisting of CD28 and ICOS.

7. A cell engineered to express a fusion protein comprising a first domain and a second domain, wherein the said domain is a polypeptide that is associated with a negative signal and said second domain is a polypeptide that is associated with a positive signal.

8. The cell of claim 7 further comprising a chimeric antigen receptor (CAR), wherein said CAR comprises an antigen recognition domain of a specific antibody and an intracellular domain of the CD3-zeta chain.

9. A vector comprising a first domain and a second domain, wherein said first domain is a polypeptide that is associated with a negative signal and said second domain is a polypeptide that is associated with a positive signal.

10. A method of treating a cancer patient, said method comprising administering to said patient a T cell genetically engineered to express a fusion protein comprising a first domain and a second domain, wherein said first domain is a polypeptide that is associated with a negative signal and said second domain is a polypeptide that is associated with a positive signal.

11. The method of claim 10, wherein said T cell is further genetically engineered to express a chimeric antigen receptor (CAR), wherein said CAR comprises an antigen recognition domain of a specific antibody and an intracellular domain of the CD3-zeta chain.

12. The method of claim 11, wherein said T cell is an autologous T cell.