Drug – bio-affecting and body treating compositions – Whole live micro-organism – cell – or virus containing – Genetically modified micro-organism – cell – or virus
Reexamination Certificate
1995-05-30
2004-07-27
Crouch, Deborah (Department: 1632)
Drug, bio-affecting and body treating compositions
Whole live micro-organism, cell, or virus containing
Genetically modified micro-organism, cell, or virus
C424S093200, C435S325000
Reexamination Certificate
active
06767535
ABSTRACT:
BACKGROUND
Cancer results when a vertebrate's own cells become malignant. Healthy individuals at any given time carry potentially malignant cells in their body. These cells are generally recognized and killed by the individuals' immune system. However, some malignant cells are not destroyed by the immune system and proliferate into tumors.
Currently, there are not adequate and specific therapies for cancer. For example, surgical excision of tumors is not an effective method of treatment where the cancer has metastasized. In addition, radiation and chemotherapy often kill normal cells in addition to cancerous cells.
Another problem is that chemotherapeutic agents follow first-order kinetics. As a result, a constant percentage, rather than a constant number of cells are killed by a given application of a chemotherapeutic agent. Consequently, malignant cells, which could cause a relapse in the disease, remain even when a patent is diagnosed as having complete clinical remission.
A method of suppressing cancer that employs the individual's own immune system would be useful.
SUMMARY OF THE INVENTION
The present invention relates to Applicant's finding that expression of the JE/MCP-1 protein in malignant cells suppresses their ability to form tumors in vivo. Thus, the invention comprises, in one embodiment, a method of suppressing tumor formation in a vertebrate by administering to the vertebrate a therapeutically effective amount of JE/MCP-1. The protein can be administered alone or as an adjuvant to surgery or cytotoxic chemotherapy.
The suppressive effect of JE/MCP-1 depends on the induction of the vertebrate's immune response, specifically the response of monocytes. Thus, in another embodiment, the invention comprises a method of increasing a vertebrate's monocyte-mediated tumoricidal activity in vivo by administering to the vertebrate an effective amount of JE/MCP-1.
JE/MCP-1 can also be administered to treat localized complications of malignancy. For example, JE/MCP-1 could be used to inhibit malignant pleural effusions or ascites. Therefore, in a further embodiment, the invention comprises methods of inhibiting pleural effusion or ascites in a vertebrate by locally administering JE/MCP-1 to the anatomic spaces between the lung and the pleural membrane or the stomach and the peritoneum.
In a further embodiment tumor killing cells, such as tumor infiltrating lymphocytes (TIL cells) are genetically engineered to express the JE/MCP-1 protein. The engineered cells therefore can be administered to a vertebrate to provide a synergistic local tumor cell killing.
In the alternative, any cell type which localizes to, or can be made to localize to a site of tumor formation can be genetically engineered to express JE/MCP-1 protein and used for gene therapy. Cells can be engineered in vivo, at the site of tumor formation, or they can be engineered Ad vitro, and subsequently administered to a vertebrate where they will express JE/MCP-1 at the site of tumor formation.
The presence of JE/MCP-1 in vivo is accompanied by a local increase in the presence of eosinophils. Therefore, another aspect of the subject invention comprises methods of combatting a parasitic infection in a vertebrate animal by administering to that vertebrate an effective amount of JE/MCP-1.
A major advantage of using JE/MCP-1 in treating cancer is that it employs the individual's own immune system and therefore would have fewer side-effects than conventional chemotherapies. In addition, JE/MCP-1 stimulates monocytes and, as such, does not depend on a total immunologic response.
REFERENCES:
patent: 4399216 (1983-08-01), Axel et al.
patent: 4477571 (1984-10-01), Chang et al.
patent: 5179078 (1993-01-01), Rollins et al.
patent: 5212073 (1993-05-01), Rollins et al.
patent: 5278287 (1994-01-01), Rollins et al.
patent: 90/07863 (1990-07-01), None
patent: 90/08777 (1990-08-01), None
patent: 90/08778 (1990-08-01), None
Crystal (1995) Science 270, 404-410.*
Vieweg et al (1995) Cancer Invest. 13, 193-201.*
Anderson (Sep. 1995) Scientific American 124-128.*
Blau et al (Nov. 2, 1995) New Eng. J. Med. 1204-1207.*
Marchall, Science 269:1050-1055, 1995.*
LaFont et al., Lancet, 346 : 1442-1443, 1995.*
Orkin et al., NIH “Repoit and Recommendations . . . ” Dec. 7, 1995, 1-40.*
Rosenberg et al, N. Eng. J. Med, vol. 323 No. 9, pp 510-57 Aug. 30, 1990.*
Bottazzi et al, Cytokine, vol. 3(5), p. 519, 1991.*
Yamaue et al., Nippon Gan Chiryo Gakkai Shi, vol. 25(5) pp. 978-989 (May 20, 1990).*
Yasuji Furutani et al., “Cloning and sequencing of the cDNA for human monocyte chemotactic and activating factor (MCAF),”Biochemical and Biophysical Reswearch Communications, 159(1):249-255 (1989).
Rollins, Barrett J. et al., “A Cell-Cycle Constraint on the Regulation of Gene Expression by Platelet-Derived Growth Factor,”Science, 238:1269-1271, (1987).
Rittling, Susan R. et al.,, “Expression of Cell cycle-dependnet genes in young and senescent WI-38 fibroblasts,”Proc. Natl. Acad. Sci. USA, 83:3316-3320, (1986).
Cochran, Brent H. et al., “Molecular Cloning of Gene Sequences Regulated by Platelet-derived Growth Factor,”Cell, 33:939-947, (1983).
Yoshimura, Teizo et al., “Human monocyte chemoattractant protein-1 MCP-1),”FEBS Letters, 244(2):487-493, (1989).
Zachariae, Claus O.C. et al., “Properties of monocyte chemotactic and activating factor (MCAF) purified from a human fibreosarcoma cell line,” Brief Definitive Report,The Journal of Experimental Medicien, 171:2177-2182 (1990).
Graves, D.T. et al., “Identification of Monocyte Chemotactic Activity Produced by Malignant Cells,”Science, 245:1490-1491, (1989).
Valente, Anthony J. et al., “Purification of a Monocyte Chemotactic factor Secreted by Nonhuman Primate Vascular Cells in Culture,”Biochemistry, 27:4162-4168 (1988).
Rollins, Barrett J. and Sunday, Mary E., “Suppression of Tumor Formation In Vivo by Expression of the JE Gene in Malignant Cells”,Molecular and Cellular Biology, 11(6):3125-3131 (1991).
Robinson, Elizabeth A. et al., “Complete amino acid sequence of a human monocyte chemoattractant, a putative mediator of cellular immune reactions”,Proc. Natl. Acad. Sci.USA, 86:1850-1854, (1989).
Rollins et al., “The Human Homolog of the JE Gene Encodes a Monocyte Secretory Protein,”Molecular and Cellular Biology, 9(11):4687-4695, (1989).
Bottazzi et al., “Monocyte Chemotactic Cytokine Gene Transfer Modulates Macrophage Infiltration, Growth and Susceptibility to IL-2 Therapy of a Murine Melanoma,”Journal of Immunology 148: 1280-1285 (1992).
Yoshimura et al., “Purification and Amino Acid Analysis of Two Human Glioma-DerivedMonocyte Chemoattractantas,”Journal of Experimental Medicine 169: 1449-1459 (1989).
Matsushima et al., “Purification and Characterization of a Novel Monocyte Chemotactic and Activating Factor Produced by a Human Myelomonocytic Cell Line,”Journl of Experimental Medicine 169: 1485-1490 (1989).
Graves et al., “Identification of Monocyte Chemotactic Activity Produced by Malignant Cells”,Science 245: 1490-1493 (1989).
Valente et al., “Purification of a Monocyte Chemotactic Factor Secreted by Nonhuman primate Vascular Cells in Culture”,Biochemistry 27: 4162-4168 (1988).
Zachariae et al., “Properties of Monocyte Chemotactic and Activating Factor (MCAF) Purified from a Human Febrosarcoma Cell Line,”Journal of Experimental Medicien 171: 2177-2182 (1990).
Rollins Barrett
Stiles Charles
Crouch Deborah
Dana-Farber Cancer Institute Inc.
Hamilton, Brook, Smith and Reynolds, P.C.
LandOfFree
Suppressing tumor formation using cells expressing... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Suppressing tumor formation using cells expressing..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Suppressing tumor formation using cells expressing... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3196589