Constitutive expression of costimulatory ligands on adoptively transferred T lymphocytes

• US 8,389,282 B2
• Filed: 03/31/2008
• Issued: 03/05/2013
• Est. Priority Date: 03/30/2007
• Status: Active Grant

• Current Assignee: Memorial Sloan-Kettering Cancer Center
• Original Assignee: Memorial Sloan-Kettering Cancer Center
• Inventors: Sadelain, Michel, Stephan, Matthias
• Primary Examiner(s): OUSPENSKI, ILIA I
• Application Number:
  US12/593,751
• Publication Number:
  US 20100178276A1
• Time in Patent Office: 1,800 Days
• Field of Search: None
• US Class Current: 435/455
• CPC Class Codes: A61K 2035/122 for inducing tolerance or supression of immune responses
• CPC Class Codes: A61K 2035/124 the cells being hematopoietic, bone marrow derived or blood cells
• CPC Class Codes: A61K 2039/5156 expressing foreign proteins
• CPC Class Codes: A61K 2039/5158 Antigen-pulsed cells, e.g. T-cells
• CPC Class Codes: A61K 2239/31 characterized by the route of administration
• 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 38/2013 IL-2
• CPC Class Codes: A61K 38/217 IFN-gamma
• CPC Class Codes: A61K 39/0011 Cancer antigens
• 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 39/464429 Molecules with a "CD" designation not provided for elsewhere
• CPC Class Codes: A61K 39/464495 Prostate specific membrane antigen [PSMA]
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 : Antimycotics
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 31/16 : for influenza or rhinoviruses
• CPC Class Codes: A61P 31/18 : for HIV
• CPC Class Codes: A61P 31/20 : for DNA viruses
• CPC Class Codes: A61P 31/22 : for herpes viruses
• CPC Class Codes: A61P 33/00 : Antiparasitic agents
• CPC Class Codes: A61P 33/02 : Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C12N 15/85 : for animal cells
• CPC Class Codes: C12N 2501/25 : Tumour necrosing factors [TNF]
• CPC Class Codes: C12N 2501/51 : B7 molecules, e.g. CD80, CD86, CD28 (ligand), CD152 (ligand)
• CPC Class Codes: C12N 2501/599 : with CD designations not provided for elsewhere
• CPC Class Codes: C12N 2510/00 : Genetically modified cells
• CPC Class Codes: C12N 2799/04 : in vivo
• CPC Class Codes: C12N 5/0636 : T lymphocytes
• CPC Class Codes: C12N 7/00 : Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention provides immunoresponsive cells, including T cells, cytotoxic T cells, regulatory T cells, and Natural Killer (NK) cells, expressing at least one of an antigen-recognizing receptor and a co-stimulatory ligand and methods of use therefore for the treatment of neoplasia and other pathologies where an increase in an antigen-specific immune response is desired.

Claims

1. An immunoresponsive cell comprising an exogenous co-stimulatory ligand and a receptor that binds an antigen, wherein the exogenous co-stimulatory ligand is 4-1BBL, a combination of 4-1BBL and CD80, or a combination of 4-1BBL and CD86, wherein the immunoresponsive cell is selected from the group consisting of a T cell, a Natural Killer (NK) cell, a cytotoxic T lymphocyte (CTL), and a regulatory T cell.

2. The immunoresponsive cell of claim 1, wherein the co-stimulatory ligand is constitutively or inducibly expressed.

3. The immunoresponsive cell of claim 2, wherein one or more co-stimulatory ligands are constitutively expressed.

4. The immunoresponsive cell of claim 1, wherein the antigen is a tumor or pathogen antigen.

5. The immunoresponsive cell of claim 4, wherein the antigen is selected from the group consisting of prostate-specific membrane antigen (PSMA), Carcinoembryonic Antigen (CEA), IL13Ralpha, her-2, CD19, NY-ESO-1, HIV-1 Gag, Lewis Y, Mart-1, gp100, tyrosinase, WT-1, hTERT, and mesothelin.

6. The immunoresponsive cell of claim 1, wherein the cell expresses a recombinant or an endogenous antigen receptor that is Pz1 or P28z.

7. The immunoresponsive cell of claim 1, wherein an endogenous or recombinant antigen receptor or antigen presenting complex is constitutively expressed on the surface of the T cell.

8. The immunoresponsive cell of claim 1, wherein the co-stimulatory ligand is constitutively expressed on the surface of the T cell.

9. The immunoresponsive cell of claim 1, wherein the co-stimulatory ligand is expressed in a retroviral vector.

10. A virus specific T cell expressing a vector encoding a polypeptide selected from the group consisting of CD80 and 4-1BBL.

11. The virus specific T cell of claim 10, wherein the T cell recognizes a virus selected from the group consisting of Cytomegalovirus (CMV), Epstein Barr Virus (EBV), Human Immunodeficiency Virus (HIV), and influenza virus antigens.

12. A tumor antigen-specific T cell expressing a vector encoding a polypeptide selected from the group consisting of CD80 and 4-1BBL.

13. The tumor antigen-specific T cell of claim 12, wherein the cell expresses CD80 and 4-1BBL.

14. The tumor antigen-specific T cell of claim 12, wherein the vector is a retroviral vector.

15. An immunoresponsive cell comprising an exogenous co-stimulatory ligand and a receptor that binds an antigen, wherein the immunoresponsive cell is a T-cell or NK cell and, wherein the the exogenous co-stimulatory ligand is 4-1BBL, a combination of 4-1BBL and CD80, or a combination of 4-1BBL and CD86.

16. An immunoresponsive cell comprising an exogenous co-stimulatory ligand and a receptor that binds an antigen, wherein the exogenous co-stimulatory ligand is 4-1BBL, a combination of 4-1BBL and CD80, or a combination of 4-1BBL and CD86, wherein the antigen is a tumor or pathogen antigen selected from the group consisting of prostate-specific membrane antigen (PSMA), Carcinoembryonic Antigen (CEA), IL13Ralpha, her-2, CD19, NY-ESO-1, HIV-1 Gag, Lewis Y, Mart-1, gp100, tyrosinase, WT-1, hTERT, and mesothelin, and wherein the immunoresponsive cell is selected from the group consisting of a T cell, a Natural Killer (NK) cell, a cytotoxic T lymphocyte (CTL), and a regulatory T cell.

17. An immunoresponsive cell comprising an exogenous co-stimulatory ligand and a receptor that binds an antigen, wherein the exogenous co-stimulatory ligand is 4-1BBL, a combination of 4-1BBL and CD80, or a combination of 4-1BBL and CD86, wherein the cell expresses a recombinant or an endogenous antigen receptor that is Pzl or P28z, and wherein the immunoresponsive cell is selected from the group consisting of a T cell, a Natural Killer (NK) cell, a cytotoxic T lymphocyte (CTL), and a regulatory T cell..

18. An immunoresponsive cell comprising an exogenous co-stimulatory ligand and a receptor that binds an antigen, wherein the exogenous co-stimulatory ligand is 4-1BBL, a combination of 4-1BBL and CD80, or a combination of 4-1BBL and CD86, wherein the co-stimulatory ligand is expressed in a retroviral vector, wherein the immunoresponsive cell is selected from the group consisting of a T cell, a Natural Killer (NK) cell, a cytotoxic T lymphocyte (CTL), and a regulatory T cell.