Treatment of diseases by site-specific instillation of cells or site-specific transformation of cells and kits therefor

• US 20020034505A1
• Filed: 09/25/2001
• Published: 03/21/2002
• Est. Priority Date: 03/31/1989
• Status: Active Grant

• 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.
• Granted Patent: US 7,238,673 B2
• Time in Patent Office: Days
• US Class Current: 424/94.2
• 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 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 2300/254 Enzymes, proenzymes
• CPC Class Codes: A61L 2300/64 Animal cells
• CPC Class Codes: A61L 2300/802 Additives, excipients, e.g. cyclodextrins, fatty acids, surfactants
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence

Abstract

A method for the direct treatment towards the specific sites of a disease is disclosed. This method is based on the delivery of proteins by catheterization to discrete blood vessel segments using genetically modified or normal cells or other vector systems. Endothelial cells expressing recombinant therapeutic agent or diagnostic proteins are situated on the walls of the blood vessel or in the tissue perfused by the vessel in a patient. This technique, provides for the transfer of cells or vectors and expression of recombinant genes in vivo and allows the introduction of proteins of therapeutic or diagnostic value for the treatment of diseases.

Claims

1. A kit for treating a disease in a patient in need thereof, comprising a catheter means and a solution which contains an enzyme of mild detergent, wherein:

(i) said catheter means is adapted for insertion into a blood vessel and comprises a main catheter body having means including a balloon element adapted to be inserted into said vessel and expansible against the walls of said vessel so as to hold said main catheter body in place in said vessel, and means carried by said main catheter body for delivering a solution into said blood vessel; and

(ii) said solution is a physiologically acceptable solution;

2. The kit of claim 1, wherein said solution contains, as said enzyme, at least one member selected from the group consisting of dispase, trypsin, collagenase, papain, pepsin, chymotrypsin, and lipases.

3. The kit of claim 1, wherein said solution contains at least one member selected from the group consisting of NP-40, Triton X100, deoxycholate, and SDS.

4. The kit of claim 1, wherein said main catheter body comprises means including two spaced balloon elements, adapted to be inserted in a blood vessel and both being expansible against the walls of the blood vessel, for providing a chamber in said blood vessel and so as to hold said main catheter body in place, and whereas said means for delivering a solution into said chamber is situated in between said balloon elements.

5. The kit of claim 1, wherein said means for delivering said solution into said blood vessel comprises a plurality of pore means.

6. A kit for treating a disease in a patient in need thereof, comprising a catheter means and a physiologically acceptable solution, wherein;

(i) said catheter means is adapted for insertion into a blood vessel and comprises a main catheter body having means including a balloon element, adapted to be inserted in said blood vessel and being expansible against the walls of said vessel so as to hold said main catheter body in place, and means carried by said main catheter body for delivering a solution into said blood vessel;

(ii) said physiologically acceptable solution comprises at least one member selected from the group consisting of heparin, poly-L-lysine, polybrene, dextransulfate, a polycationic material, and bivalent antibodies.

7. The kit of claim 6, wherein said physiologically acceptable solution further comprises DNA.

8. The kit of claim 6, wherein said physiologically acceptable solution further comprises a growth factor.

9. A method for treating a disease in a patient in need thereof, comprising causing a cell attached onto the walls of a vessel or in an organ or tissue in said patient to express an exogeneous therapeutic agent protein, wherein said protein treats said disease.

10. The method of claim 9, wherein said disease is an ischemic disease, a vasomotor disease, diabetes, a malignancy, AIDS or a genetic disease

11. The method of claim 9, wherein said disease is a systemic disease.

12. The method of claim 9, wherein said exogeneous therapeputic agent protein is one member selected from the group consisting of tPA and modifications thereof, urokinase, streptokinase, acidic fibroblast growth factor, basic fibroblast growth factor, tumor necrosis factor α

, tumor necrosis factor β

, transforming growth factor α

, transforming growth factor β

, atrial natriuretic factor, platelet-derived growth factor, endothelian, insulin, diphtheria toxin, pertussis toxin, cholera toxin, soluble CD4 and derivatives thereof, and growth hormone.

13. The method of claim 9, wherein said cell is selected from the group consisting of endothelial cells, vascular smooth muscle cells, fibroblasts, connective tissue cells, macrophages, monocytes, and parenchymal cells.

15. The method of claim 14, wherein said cells are transformed cells.

16. The method of claim 14, wherein said cells are normal cells.

18. The method of claim 17, wherein said disease is a malignancy associated with a tumor, and wherein said cells are transformed with a DNA sequence or an RNA sequence encoding an intracellular, secreted, or cell surface molecule which is (1) exogenous to said patient and which is (2a) immunogenic to said patient, (2b) induces rejection, regression, or both of said tumor, or (2c) toxic to the cells of said tumor.

19. The method of claim 18, wherein said molecule is immunogenic to said patient.

20. The method of claim 18, wherein said molecule induces rejection, regression, or both, of said tumor.

21. The method of claim 20, wherein said molecule is a growth stimulant or inhibitor.

22. The method of claim 20, wherein said molecule is an inducer of cellular differentiation.

23. The method of claim 18, wherein said molecule is toxic to the cells of said tumor.

24. The method of claim 18, wherein said DNA or RNA sequence is obtained from a species which is the same as said patient.

25. The method of claim 18, wherein said DNA or RNA sequence is obtained from a species different than the species of said patient.

26. The method of claim 18, wherein said DNA or RNA sequence is administered locally to said patient in a viral vector.

27. The method of claim 18, wherein said DNA or RNA sequence is administered locally to said patient as a DNA or RNA/liposome complex.

28. The method of claim 18, wherein said DNA or RNA sequence is administered locally to said patient via a cell line.

29. The method of claim 18, wherein said DNA or RNA sequence is administered to said patient systemically as a chemical formulation containing said DNA or RNA sequence coupled to a carrier molecule which facilitates delivery of said sequence to target cells in said patient.

30. The method of claim 18, wherein said DNA or RNA sequence is one member selected from the group consisting of Class I histocompatibility genes, Class II histocompatibility genes, bacterial genes encoding peptides having immunostimulant properties, genes encoding viral glycoproteins having immunostimulant properties, genes encoding minor histocompatibility antigens, genes encoding lysozymes or bovine serum albumin, and oncogenes.

31. The method of claim 18, wherein said DNA or RNA sequence is one member selected from the group consisting of DNA or RNA sequences encoding interleukin-1, 2, 3, 4, 6 or 8, TNF-α

or β

, TGF-β

(1, 2 or

     3), soluble growth factors, recombinant antibodies to growth factors or receptors or analogues thereof, interferon α

, β

or γ

, and adhesion molecules.

32. The method of claim 18, wherein said DNA or RNA sequence is one member selected from the group consisting of DNA and RNA sequences encoding thymidine kinase, diphtheria toxin, pertussis toxin or drug-sensitive proteins.

14. A method for treating a disease, comprising site-specifically instilling cells.

17. A method for treating a disease, in a patient comprising site-specifically transforming cells in vivo.