UNIVERSAL IMMUNE CELLS FOR CANCER IMMUNOTHERAPY

• US 20180085399A1
• Filed: 01/26/2016
• Published: 03/29/2018
• Est. Priority Date: 01/26/2015
• Status: Active Grant

• Current Assignee: Baylor College of Medicine (Baylor College)
• Original Assignee: Baylor College of Medicine (Baylor College)
• Inventors: Ahmed, Nabil M., Bielamowicz, Kevin, Fousek, Kristen
• Granted Patent: US 11,219,644 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 2035/124 the cells being hematopoietic, bone marrow derived or blood cells
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2239/26 Universal/off- the- shelf cellular immunotherapy; Allogenic cells or means to avoid rejection
• 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 2239/47 Brain; Nervous system
• CPC Class Codes: A61K 35/00 Medicinal preparations containing materials or reaction products thereof with undetermined constitution
• 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 39/464406 Her-2/neu/ErbB2, Her-3/ErbB3 or Her 4/ ErbB4
• CPC Class Codes: A61K 39/464419 Receptors for interleukins [IL]
• CPC Class Codes: A61K 39/464422 Ephrin Receptors [Eph]
• 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 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: C07K 14/7051 T-cell receptor (TcR)-CD3 complex
• 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 16/2866 against receptors for cytokines, lymphokines, interferons
• CPC Class Codes: C07K 16/32 against translation products of oncogenes
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• 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: C12N 15/86 : Viral vectors
• CPC Class Codes: C12N 2740/10043 : viral genome or elements thereof as genetic vector
• CPC Class Codes: G01N 33/574 : for cancer

Abstract

Embodiments of the disclosure encompass adoptive immunotherapy related to cells expressing multiple chimeric antigen receptors (CARs). In specific embodiments, T cells express a HER2-specific CAR, an IL13 Rα2-specific CAR, and an EphA2-specific CAR. In particular embodiments, the cells are utilized for cancer treatment, including for glioblastoma.

Claims

1. A composition comprising:

a) an expression construct that encodes a HER2-specific chimeric antigen receptor (CAR);

b) an expression construct that encodes an IL13Rα

2 CAR; and

c) an expression construct that encodes an EphA2 CAR,

wherein there is one of the following;

1) the expression construct of a) and b) and c) are located on separate molecules;

2) the expression construct of a) and b) are the located on same molecule;

3) the expression construct of a) and c) are located on the same molecule;

4) the expression construct of b) and c) are located on the same molecule;

or

5) the expression construct of a), b), and c) are located on the same molecule.

2. The composition of claim 1, wherein the expression construct of a), b), and/or c) are located on a vector.

3. The composition of claim 1, wherein for the expression constructs of 2), 3), 4), or 5), the CARs of the expression constructs are expressable as a single open reading frame.

4. The composition of claim 2, wherein the expression vector further comprise sequence that encodes an inducible suicide gene.

5. The composition of claim 3, wherein the vector is a non-viral vector or a viral vector.

6. The composition of claim 5, wherein the viral vector is a retroviral vector, lentiviral vector, adenoviral vector, or adeno-associated viral vector.

7. The composition of claim 1, wherein the CAR comprises an intracellular signaling domain selected from the group consisting of CD28, OX40, 4-1BB, ICOS and a combination thereof.

8. The composition of claim 1, wherein one or more of the CARs comprises a transmembrane domain selected from the group consisting of CD3-zeta and CD28.

9. The composition of claim 4, wherein the suicide gene is selected from the group consisting of caspase 9, herpes simplex virus, thymidine kinase (HSV-tk), cytosine deaminase (CD) and cytochrome P450.

10. A cell comprising the composition of any of claim 1.

11. The cell of claim 10, wherein the expression constructs of a), b), and c) are separate entities.

12. The cell of claim 10, wherein the cell is a eukaryotic cell.

13. The cell of claim 10, wherein the cell is a human cell.

14. The cell of claim 10, wherein the cell is an immune cell.

15. The cell of claim 10, wherein the cell is autologous, syngeneic, allogeneic, or xenogeneic in relation to a particular individual.

16. The cell of claim 15, wherein the individual is in need of cancer treatment.

17. The cell of claim 15, wherein the individual is in need of treatment for glioblastoma.

18. The cell of claim 10, further defined as a cytotoxic T lymphocyte (CTL), natural killer cell, or natural killer T cell.

19. The cell of claim 10, wherein the cell comprises at least one other CAR specific for an antigen other than HER2, IL13Rα

2, or EphA2.

20. The cell of claim 19, wherein the CAR is specific for an antigen selected from the group consisting of Melanoma-associated antigen (MAGE), Preferentially expressed antigen of melanoma (PRAME), survivin, CD19, CD20, CD22, k light chain, CD30, CD33, CD123, CD38, ROR1, ErbB2, ErbB3/4, ErbB dimers, EGFr vIII, carcinoembryonic antigen, EGP2, EGP40, mesothelin, TAG72, PSMA, NKG2D ligands, B7-H6, MUC1, MUC16, CA9, GD2, GD3, HMW-MAA, CD171, Lewis Y, G250/CAIX, HLA-AI MAGE A1, HLA-A2 NY-ESO-1, PSCA, folate receptor-a, CD44v6, CD44v7/8, a_vb₆ integrin, 8H9, NCAM, VEGF receptors, 5T4, Foetal AchR, NKG2D ligands, CD44v6, dual antigen, and universal.

21. A method of treating cancer in an individual, comprising the step of delivering to the individual a therapeutically effective amount of the composition of claim 1.

22. A method of treating cancer in an individual, comprising the step of delivering to the individual a therapeutically effective amount of the cells of claim 10.

23. The method of claim 22, wherein the individual has a cancer that expresses HER2, IL13Rα

2, and EphA2.

24. The method of claim 22, wherein the cancer is glioblastoma.

25. The method of claim 22, comprising the step of analyzing a sample comprising cancer cells from the individual for one or more antigens on one or more cancer cells.

26. The method of claim 25, wherein the cells comprising the composition are produced to target one or more particular antigens based on an outcome of the analyzing step.

27. A kit comprising a composition of claim 1.

28. A kit comprising cells of claim 10.