Site-specific instillation of cells or site-specific transformation of cells and kits therefor

• US 6,297,219 B1
• Filed: 07/08/1997
• Issued: 10/02/2001
• Est. Priority Date: 03/31/1989
• Status: Expired due to Term

• Current Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Original Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Inventors: Nabel, Gary J., Nabel, Elizabeth G.
• Primary Examiner(s): Hauda, Karen M.
• Assistant Examiner(s): WEHBE, ANNE MARIE SABRINA
• Application Number:
  US08/889,399
• Time in Patent Office: 1,547 Days
• Field of Search: 514/44, 424/93.21, 435/375
• US Class Current: 514/44.00R
• CPC Class Codes: A61B 17/22 Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for dilators A61M29/00
• CPC Class Codes: A61B 2017/22038 with a guide wire
• CPC Class Codes: A61B 2017/22054 with two balloons
• CPC Class Codes: A61B 2017/22082 after introduction of a substance
• CPC Class Codes: A61B 2017/22084 stone- or thrombus-dissolving
• CPC Class Codes: A61K 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 47/6957 the form being a device or a kit, e.g. stents or microdevices
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/258 Genetic materials, DNA, RNA, genes, vectors, e.g. plasmids
• CPC Class Codes: A61L 2300/626 Liposomes, micelles, vesicles
• CPC Class Codes: A61L 2300/64 Animal cells
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence

Abstract

A method for the direct in vivo transformation of cells in and surrounding a solid tumor is disclosed. This method is based on the site-specific delivery of proteins to solid tumors and to tissue surrounding the solid tumor by direct injection of a nucleic acid sequence. In particular, this method is directed to site-specific delivery of nucleic acids encoding major histocompatibility proteins, cytokines, and toxins to a solid tumor. This technique provides for the transfer of vectors and expression of recombinant genes in vivo and allows the introduction of proteins of therapeutic or diagnostic value for the treatment of disease.

Claims

1. A method of transforming cells surrounding a solid tumor in a mammal, which comprises directly injecting into said solid tumor a viral vector containing a nucleic acid sequence encoding a protein selected from the group consisting of a Class I histocompatibility protein, a Class II histocompatibility protein, a cytokine, diphtheria toxin, and pertussis toxin in an amount effective for transforming said cells, wherein said protein is expressed by said cells.

2. A method of in vivo site-specifically transforming cells in a solid tumor in a mammal, or in tissues surrounding said solid tumor, which comprises introducing into said mammal by direct injection at said solid tumor a viral vector containing a nucleic acid sequence encoding a protein selected from the group consisting of a Class I histocompatibility protein, a Class II histocompatibility protein, a cytokine, diphtheria toxin, and pertussis toxin in an amount effective for transforming said cells or tissues, such that cells or tissues express said protein.

3. The method of claim 2, wherein said protein is immunogenic to said patient.

4. The method of claim 2, wherein said protein induces cellular differentiation.

5. The method of claim 2, wherein said nucleic acid sequence is obtained from a species which is the same as said mammal.

6. The method of claim 2, wherein said nucleic acid sequence is obtained from a species different than the species of said mammal.

7. The method of claim 2, wherein said nucleic acid sequence is administered as a nucleic acid/liposome complex.

8. The method of claim 2, wherein said protein is selected from the group consisting of a Class I histocompatibility protein and a Class II histocompatibility protein.

9. The method of claim 2, wherein said cytokine is selected from the group consisting of interleukin-1, interleukin-2, interleukin-3, interleukin-4, interleukin-6, interleukin-8, tumor necrosis factor-α

, tumor necrosis factor-β

1, tumor necrosis factor-β

2, tumor necrosis factor-β

3, interferon α

, interferon β

, and interferon γ

.

10. The method of claim 2, wherein said protein is selected from the group consisting of diphtheria toxin, and pertussis toxin.

11. The method of claim 2, wherein said nucleic acid encodes a cytokine selected from the group consisting of interleukin-1, interleukin-2, interleukin-3, interleukin-4, interleukin-6, interleukin-8, tumor necrosis factor-α

, tumor necrosis factor-β

1, tumor necrosis factor-β

2, tumor necrosis factor-β

3, interferon α

, and interferon β

.

12. The method of claim 11, wherein said nucleic acid sequence encodes interleukin-2.

13. The method of claim 2, wherein said viral vector is an adenoviral vector.

14. A method of in vivo site-specifically transforming cells in a solid tumor in a mammal, or in tissues surrounding said solid tumor, which comprises introducing into said mammal by direct injection at said solid tumor a nucleic acid sequence encoding a protein selected from the group consisting of a Class I histocompatibility protein, a Class II histocompatibility protein, a cytokine, diphtheria toxin, and pertussis toxin in an amount effective for transforming said cells or tissues, such that cells or tissues express said protein.

15. The method of claim 14, wherein said protein is immunogenic to said patient.

16. The method of claim 14, wherein said protein induces cellular differentiation.

17. The method of claim 14, wherein said nucleic acid sequence is obtained from a species which is the same as said mammal.

18. The method of claim 14, wherein said nucleic acid sequence is obtained from a species different than the species of said mammal.

19. The method of claim 14, wherein said nucleic acid sequence is administered as a nucleic acid/liposome complex.

20. The method of claim 14, wherein said protein is selected from the group consisting of a Class I histocompatibility protein and a Class II histocompatibility protein.

21. The method of claim 14, wherein said cytokine is selected from the group consisting of interleukin-1, interleukin-2, interleukin-3, interleukin-4, interleukin-6, interleukin-8, tumor necrosis factor-α

, tumor necrosis factor-β

1, tumor necrosis factor-β

2, tumor necrosis factor-β

3, interferon α

, interferon β

, and interferon γ

.

22. The method of claim 14, wherein said protein is selected from the group consisting diphtheria toxin, and pertussis toxin.

23. The method of claim 14, wherein said nucleic acid encodes a cytokine selected from the group consisting of interleukin-1, interleukin-2, interleukin-3, interleukin-4, interleukin-6, interleukin-8, tumor necrosis factor-α

, tumor necrosis factor-β

1, tumor necrosis factor-β

2, tumor necrosis factor-β

3, interferon α

, and interferon β

.

24. The method of claim 23, wherein said nucleic acid sequence encodes interleukin-2.