Compositions for treatment of cancer

• US 8,911,993 B2
• Filed: 07/10/2013
• Issued: 12/16/2014
• Est. Priority Date: 12/09/2010
• 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., Levine, Bruce L., Porter, David L., Kalos, Michael D., Milone, Michael C.
• Primary Examiner(s): BURKHART, MICHAEL D
• Application Number:
  US13/938,923
• Publication Number:
  US 20130288368A1
• Time in Patent Office: 524 Days
• Field of Search: None
• US Class Current: 435/372.3
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/5256 expressing foreign proteins
• CPC Class Codes: A61K 2039/585 wherein the target is cancer
• CPC Class Codes: A61K 2239/31 characterized by the route of administration
• 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 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/177 Receptors; Cell surface antigens; Cell surface determinants
• 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 39/39558 against tumor tissues, cells, 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 39/464412 CD19 or B4
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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 35/02 specific for leukemia
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/075 : Adenoviridae
• CPC Class Codes: C07K 14/525 : Tumour necrosis factor [TNF]
• CPC Class Codes: C07K 14/7051 : T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C07K 14/70517 : CD8
• CPC Class Codes: C07K 14/70521 : CD28, CD152
• CPC Class Codes: C07K 14/70578 : NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 NGF-receptor C07K14/71, TNF-receptor C07K14/7151
• CPC Class Codes: C07K 14/70596 : Molecules with a "CD"-designation not provided for elsewhere
• CPC Class Codes: C07K 16/2803 : against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/2896 : against molecules with a "CD"-designation, not provided for elsewhere
• CPC Class Codes: C07K 16/30 : from tumour cells
• CPC Class Codes: C07K 16/3061 : Blood cells
• CPC Class Codes: C07K 2317/53 : Hinge
• CPC Class Codes: C07K 2317/622 : Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/76 : Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/80 : remaining in the (producing) cell, i.e. intracellular antibodies or intrabodies
• CPC Class Codes: C07K 2319/00 : Fusion polypeptide
• CPC Class Codes: C07K 2319/02 : containing a signal sequence
• CPC Class Codes: C07K 2319/03 : containing a transmembrane segment
• CPC Class Codes: C07K 2319/30 : Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
• CPC Class Codes: C07K 2319/33 : fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
• CPC Class Codes: C07K 2319/74 : containing a fusion for binding to a cell surface receptor
• CPC Class Codes: C12N 15/85 : for animal cells
• CPC Class Codes: C12N 15/861 : Adenoviral vectors
• CPC Class Codes: C12N 2501/51 : B7 molecules, e.g. CD80, CD86, CD28 (ligand), CD152 (ligand)
• CPC Class Codes: C12N 2501/515 : CD3, T-cell receptor complex
• CPC Class Codes: C12N 2510/00 : Genetically modified cells
• CPC Class Codes: C12N 2740/15034 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2740/15043 : viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2740/15071 : Demonstrated in vivo effect
• 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

Abstract

The present invention provides compositions and methods for treating cancer in a human. The invention includes relates to administering a genetically modified T cell to express 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 pharmaceutical composition comprising an anti-tumor effective amount of a population of human T cells, wherein the T cells comprise a nucleic acid sequence that encodes a chimeric antigen receptor (CAR), wherein the CAR comprises a CD19 antigen binding domain comprising the amino acid sequence of SEQ ID NO:

20, a CD8α

hinge domain, a CD8α

transmembrane domain, a 4-1BB costimulatory signaling region, and a CD3 zeta signaling domain comprising the amino acid sequence of SEQ ID NO;

24, wherein the T cells are T cells of a human having a cancer.

2. The composition of claim 1, wherein the anti-tumor effective amount of T cells is 10⁴ to 10⁹ cells per kg body weight of a human in need of such cells.

3. The composition of claim 1, wherein the CD8α

transmembrane domain comprises the amino acid sequence of SEQ ID NO;

22.

4. The composition of claim 1, wherein the CD8α

hinge domain comprises the amino acid sequence of SEQ ID NO;

21.

5. The composition of claim 1, wherein the 4-1BB costimulatory signaling region comprises the amino acid sequence of SEQ ID NO:

23.

6. The composition of claim 1, wherein the CD19 antigen binding domain is encoded by a nucleic acid sequence comprising SEQ ID NO:

14.

7. The composition of claim 3, wherein the CD8α

transmembrane domain is encoded by a nucleic acid sequence comprising SEQ ID NO;

16.

8. The composition of claim 4, wherein the CD8α

hinge domain is encoded by a nucleic acid sequence comprising SEQ ID NO;

15.

9. The composition of claim 5, wherein the 4-1BB costimulatory signaling region is encoded by a nucleic acid sequence comprising SEQ ID NO:

17.

10. The composition of claim 1, wherein the CD3 zeta signaling domain is encoded by a nucleic acid sequence comprising SEQ ID NO:

18.

11. The composition of claim 3, wherein the 4-1BB costimulatory signaling region comprises the amino acid sequence of SEQ ID NO:

23.

12. The composition of claim 11, wherein the 4-1BB costimulatory signaling region of the CAR is encoded by a nucleic acid sequence comprising SEQ ID NO:

17.

13. The composition of claim 4, wherein the 4-1BB costimulatory signaling region comprises the amino acid sequence of SEQ ID NO:

23.

14. The composition of claim 13, wherein the 4-1BB costimulatory signaling region is encoded by a nucleic acid sequence comprising SEQ ID NO:

17.

19. The composition of claim 1, wherein the anti-tumor effective amount of T cells is 10⁵ to 10⁶ cells per kg body weight of a human in need of such cells.

20. The composition of claim 3, wherein the CD8α

hinge domain comprises the amino acid sequence of SEQ ID NO;

21.

21. The composition of claim 20, wherein the CD8α

hinge domain is encoded by a nucleic acid sequence comprising SEQ ID NO;

15.

15. A pharmaceutical composition comprising an anti-tumor effective amount of a population of human T cells, wherein the T cells comprise a nucleic acid sequence that encodes a chimeric antigen receptor (CAR), wherein the CAR comprises a CD19 antigen binding domain comprising the amino acid sequence of SEQ ID NO:

20, a CD8α

hinge domain comprising the amino acid sequence of SEQ ID NO;

21, a CD8α

transmembrane domain comprising the amino acid sequence of SEQ ID NO;

22, a 4-1BB costimulatory signaling region comprising the amino acid sequence of SEQ ID NO;

23, and a CD3 zeta signaling domain comprising the amino acid sequence of SEQ ID NO;

24, wherein the T cells are T cells of a human having a cancer.

16. The composition of claim 15, wherein the CD19 antigen binding domain of the CAR is encoded by a nucleic acid sequence comprising SEQ ID NO:

14, the CD8α

hinge domain of the CAR is encoded by a nucleic acid sequence comprising SEQ ID NO;

15, the CD8α

transmembrane domain of the CAR is encoded by a nucleic acid sequence comprising SEQ ID NO;

16, the 4-1BB costimulatory signaling region of the CAR is encoded by a nucleic acid sequence comprising SEQ ID NO;

17, and the CD3 zeta signaling domain of the CAR is encoded by a nucleic acid sequence comprising SEQ ID NO;

18.

17. The composition of claim 15, wherein the anti-tumor effective amount of T cells is 10⁴ to 10⁹ cells per kg body weight of a human in need of such cells.

18. The composition of claim 15, wherein the anti-tumor effective amount of T cells is 10⁵ to 10⁶ cells per kg body weight of a human in need of such cells.