ENGINEERED CD19-SPECIFIC T LYMPHOCYTES THAT COEXPRESS IL-15 AND AN INDUCIBLE CASPASE-9 BASED SUICIDE GENE FOR THE TREATMENT OF B-CELL MALIGNANCIES

• US 20130071414A1
• Filed: 04/27/2012
• Published: 03/21/2013
• Est. Priority Date: 04/27/2011
• Status: Abandoned Application

• Current Assignee: Baylor College of Medicine (Baylor College)
• Original Assignee: Baylor College of Medicine (Baylor College)
• Inventors: Spencer, David M., Rooney, Cliona M., Brenner, Malcolm K., Dotti, Gianpietro
• Application Number:
  US13/458,085
• Publication Number:
  US 20130071414A1
• Time in Patent Office: Days
• US Class Current: 424/184.1
• 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 38/20 Interleukins [IL]
• 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 39/4635 Cytokines
• CPC Class Codes: A61K 39/464412 CD19 or B4
• CPC Class Codes: C12N 15/85 for animal cells
• CPC Class Codes: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 15/861 Adenoviral vectors
• CPC Class Codes: C12N 15/8645 Adeno-associated virus
• CPC Class Codes: C12N 15/867 Retroviral vectors
• CPC Class Codes: C12N 2740/13043 viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2840/20 translation of more than one cistron
• CPC Class Codes: C12N 5/0636 T lymphocytes
• CPC Class Codes: C12N 5/0638 Cytotoxic T lymphocytes [CTL] or lymphokine activated killer cells [LAK]
• CPC Class Codes: C12N 5/0646 Natural killers cells [NK], NKT cells

Abstract

The present invention generally concerns particular methods and compositions for cancer therapy. In particular embodiments, there methods and compositions related to cells that harbor expression vectors encoding a cytokine and an inducible suicide gene and, optionally, the same or different vector(s) encoding a chimeric antigen receptor and/or a detectable gene product.

Claims

1. An isolated polynucleotide, comprising a cytokine, an inducible suicide gene, and one or both of the following:

a) a detectable gene product;

or

b) a chimeric antigen receptor.

2. The polynucleotide of claim 1, further defined as comprising a vector.

3. The polynucleotide of claim 2, wherein the vector is a viral vector or a plasmid.

4. The polynucleotide of claim 3, wherein the viral vector is an adenoviral vector, a retriviral vector, a lentiviral vector, or an adeno-associated viral vector.

5. The polynucleotide of claim 1, wherein the cytokine is IL-15, IL-2, IL-7, IL-12, or IL-21.

6. The polynucleotide of claim 1, wherein the inducible suicide gene is non-immunogenic to humans.

7. The polynucleotide of claim 6, wherein the inducible suicide gene is caspase 9.

8. The polynucleotide of claim 1, wherein the chimeric antigen receptor targets CD19.

9. The polynucleotide of claim 1, wherein the chimeric antigen receptor has a costimulatory endodomain from CD28, 4-IBB, OX40, or a combination thereof.

10. The polynucleotide of claim 1, wherein the detectable gene product is a nonfunctional gene product.

11. The polynucleotide of claim 1, wherein the detectable gene product is Δ

NGFR, a truncated form of CD19, or a truncated form of CD34.

12. A mammalian cell, comprising the polynucleotide of claim 1.

13. The cell of claim 12, wherein the cell is a T lymphocyte, natural killer cell, lymphokine-activated killer cell, or tumor infiltrating lymphocyte.

14. A method of inhibiting proliferation of a cancer cell in an individual, comprising the step of delivering to the individual a therapeutically effective amount of cells of claim 13.

15. The method of claim 14, further defined as:

delivering to the individual a therapeutically effective amount of cells of claim 13;

releasing a relevant T cell growth factor or immunomodulating cytokine locally in the tumor microenviroment; and

eliminating the cells upon exposure to the inducible gene product.

16. A kit comprising the polynucleotide of claim 1.

17. A kit comprising one or more cells of claim 12.

18. A method of making a cell of claim 12, comprising the step of introducing to the cell a polynucleotide comprising a cytokine, an inducible suicide gene, and one or both of the following:

a) a detectable or selectable gene product;

or

b) a chimeric antigen receptor.