Combined Gene Therapy for the Treatment of Macroscopic Gliomas

• US 20080181870A1
• Filed: 08/12/2005
• Published: 07/31/2008
• Est. Priority Date: 08/12/2004
• Status: Active Grant

• Current Assignee: Cedars-Sinai Medical Center (Cedars Sinai Health System)
• Original Assignee: Cedars-Sinai Medical Center (Cedars Sinai Health System)
• Inventors: Lowenstein, Pedro, Castro, Maria
• Granted Patent: US 8,420,611 B2
• Time in Patent Office: Days
• US Class Current: 424/93.2
• CPC Class Codes: A01K 2267/0331 Animal model for proliferative diseases
• 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 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61K 35/761 Adenovirus
• CPC Class Codes: A61K 38/18 Growth factors; Growth regulators
• 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: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 2710/10332 Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
• CPC Class Codes: C12N 2710/10343 viral genome or elements thereof as genetic vector

Abstract

Described herein are compositions and methods for the treatment of cancer, and particularly brain cancer (e.g., glioma) in a mammal. In various embodiments of the invention, a combined therapeutic approach including TK with systemic ganciclovir administration and Flt3L are used in connection with gene therapeutic techniques or direct peptide injection for the aforementioned indications. Kits useful in practicing the inventive method are also disclosed, as are animal models useful for studying brain cancer.

Claims

1. A method for treating cancer in a mammal, comprising:

providing a quantity of a viral vector expressing TK;

providing a quantity of a viral vector expressing Flt3L;

administering a therapeutically effective amount of the quantity of the viral vector expressing TK and the quantity of the viral vector expressing Flt3L to the mammal; and

administering a therapeutically effective quantity of systemic ganciclovir to the mammal.

2. The method of claim 1, wherein the viral vectors are each independently selected from the group consisting of recombinant adenoviral vectors, recombinant adeno-associated viral vectors, herpes simplex virus type 1 vectors, and lentiviral vectors.

3. The method of claim 1, wherein the viral vector expressing TK is a recombinant adenoviral vector.

4. The method of claim 1, wherein the viral vector expressing Flt3L is a herpes simplex virus type-1 vector.

5. The method of claim 1, wherein the cancer is brain cancer.

6. A method for treating cancer in a mammal, comprising:

providing a quantity of a viral vector expressing TK;

providing a composition comprising Flt3L protein;

administering a therapeutically effective amount of the quantity of the viral vector expressing TK and the composition comprising Flt3L protein to the mammal; and

administering a therapeutically effective quantity of systemic ganciclovir to the mammal.

7. The method of claim 6, wherein the composition further comprises a pharmaceutically acceptable carrier.

8. The method of claim 6, wherein the viral vector is selected from the group consisting of recombinant adenoviral vectors, recombinant adeno-associated viral vectors, herpes simplex virus type 1 vectors, and lentiviral vectors.

9. The method of claim 6, wherein the viral vector expressing TK is a recombinant adenoviral vector.

10. The method of claim 6, wherein the cancer is brain cancer.

11. A kit, comprising:

a composition comprising a viral vector expressing TK;

a composition comprising a viral vector expressing Flt3L;

instructions for the use of said compositions for treating cancer in a mammal.

12. The kit of claim 11, further comprising a quantity of ganciclovir.

13. A kit, comprising:

a composition comprising a viral vector expressing TK;

a composition comprising Flt3L peptide;

instructions for the use of said compositions for treating cancer in a mammal.

14. The kit of claim 13, further comprising a quantity of ganciclovir.

15. An animal model for brain cancer, comprising a non-human mammal, wherein the non-human mammal carries in at least a portion of the cells of its brain at least one exogenous TK DNA and at least one exogeneous Flt3L DNA.