Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1995-12-01
1999-06-08
Stanton, Brian R.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
4353201, 4351723, 435 691, 435375, 935 56, 935 71, 935 33, A61K 4800, C12N 1563, C12N 1579, C12N 1509
Patent
active
059104880
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention pertains to plasmids suitable for gene therapy and related methods.
BACKGROUND OF THE INVENTION
A variety of genetic abnormalities arise in human cancer that contribute to neoplastic transformation and malignancy. Instability of the genome generates mutations that alter cell proliferation, angiogenesis, metastasis, and tumor immunogenicity. Despite a better understanding of the molecular basis of cancer, many malignancies remain resistant to traditional forms of treatment. The definition of tumor-associated genetic mutations, however, has heightened interest in cancer as a target for gene therapy. Immunotherapy has shown promise as a primary approach to the treatment of malignancy. Indeed, specific cancers, such as melanoma or renal cell carcinoma, are relatively more responsive to modulation of immune function, possibly because the immune system can be induced to recognize mutant gene products in these cells. Conventionally, approaches to immunotherapy have involved the administration of non-specific immunomodulating agents such as Bacillus Calmette-Guerin (BCG), cytokines, and/or adoptive T cell transfer, which have shown promise in animal models (B. Zbar, et al., J. Natl. Canc. Inst. 46, 831 (1971); S. A. Rosenberg, et al., J. Exp. Med. 16, 1169 (1985); S. Shu, and S. A. Rosenberg, Cancer Res. 45, 1657 (1985); P. J. Spiess, et al., J. Natl. Canc. Inst. 79, 1067; T. Chou, et al., J. Immunol. 140, 2453 (1988); H. Yoshizawa, et al., J. Immunol. 147, 729 (1991)) and in man (D. L. Morton, et al., Ann. Surg. 180, 635 (1974); S. A. Rosenberg, et al., Ann. Surg. 210, 474 (1989); S. A. Rosenberg, et al., N. Eng. J. Med. 319, 1676 (1988); R. L. Kradin, et al., Lancet 577 (1989)). More recently, molecular genetic interventions have been designed in an attempt to improve the efficacy of immunotherapy. Human gene transfer protocols have been designed to monitor the traffic of lymphocytes into melanoma tumors (S. A. Rosenberg, et al., N. Eng. J. Med. 323, 570 (1990)) or to introduce cytokine genes into tumor cells to stimulate the host's immune response to residual tumor (S. A. Rosenberg, Hum. Gene Ther. 3, 57 (1992)).
Recently, a new molecular genetic intervention has been developed for human malignancy. This approach relies on the direct transmission of recombinant genes into established tumors in vivo to genetically modify them as they grow in situ. In animal models, introduction of a gene encoding a foreign major histocompatibility (MHC) protein (class I) in vivo signals the immune system to respond to the foreign antigen (G. E. Plautz, et al., Proc. Natl. Acad. Sci. USA 90, 4645 (1993); E. G. Nabel, et al., Proc. Natl. Acad. Sci. USA 89, 5157 (1992)). More importantly, when this gene is transduced into established tumors in vivo, a cytolytic T cell response is also generated against unmodified tumor cells. In murine models, this approach has led to significant reductions in tumor growth and, in some cases, complete remission (G. E. Plautz, et al., Proc. Natl. Acad. Sci. USA 90, 4645 (1993)). Based on these studies, approval was recently received from the Recombinant DNA Advisory Committee of the National Institutes of Health to conduct a human clinical protocol using direct transfer of a human transplantation antigen gene in an effort to treat malignancy. This protocol proposed to perform direct gene transfer in humans and to utilize a non-viral vector which reduces several safety concerns about viral vectors. This clinical trial involved the treatment of patients with metastatic melanoma at subcutaneous lesions. The treatment constituted intratumoral injection of the human class I MHC gene, HLA-B7, complexed to a cationic liposome, DC-Cholesterol (G. J. Nabel, Hum. Gene Ther. 3, 705 (1992); X. Gao and L. Huang, Biochem. Biophys. Res. Commun. 179, 280 (1991)). These patients received escalating doses of the DNA liposome complex. Recombinant gene expression, toxicity, and the immunologic response to treatment is being evaluated. Based on animal studies, no toxiciti
REFERENCES:
patent: 5580859 (1996-12-01), Felgner
Alexander, P. (1973) Activated macrophages and the antitumor action of BCG. Natl. Cancer Inst. Monogr. 39:127-133.
Barbosa, J. et al. (1982) Identification of human genomic clones coding the major histocompatibility antigens HLA-A2 and HLA-B7 by DNA-mediated gene transfer. Proc. Natl. Acad. Sci. 79:6327-6331.
Bjorkman, P.J. et al (1990) Structure, function, and diversity of class 1 major histocompatibility complex molecules. Annu. Rev. Biochem. 59:253-288.
Canonico, A., et al. (1991) Expression of a CMV promoter driven human .alpha.-1 antitrypsin gene in cultured lung endothelial cells and in the lungs of rabbits. Clinical Research 39(2):219A.
Carlow, D.A. et al. (1989) Failure of expression of class I major histocompatibility antigens to alter tumor immunogenicity of a spontaneous murine carcinoma. J. Natl. Canc. Inst. 81:759-767.
Chamberlain, J., et al. (1988) Tissue-specific and cell surface expression of human major histocompatibility complex class I heavy (HLA-B7) and light .beta..sub.2 -microglobulin) chain genes in transgenic mice. Proc. Natl. Acad. Sci. 85:7690-7694.
Chou, T. et al. (1988) Generation of therapeutic T lymphocytes from tumor-bearing mice by in vitro sensitization. Culture requirements and characterization of immunologic specificity. J. Immunol. 140:2453-2461.
Clark, S.C. et al. (1987) The human hematopoietic colony-stimulating factors. Science 236:1229-1237.
Cole, G.A. et al. (1987) Allogeneic H-2 antigen expression is insufficient for tumor rejection. Proc. Natl. Acad. Sci. USA 84:8613-8617.
Fearon, E.R. et al. (1990) Interleukin-2 production by tumor cells bypasses T helper function in the generation of an antitumor response. Cell 60:397-403.
Felgner, P.L. et al. (1987) Lipofection: A highly efficient, lipid-mediated DNA-transfection procedure. Proc. Natl. Acad. Sci. 84:7413-7417.
Felgner, P.L. et al. (1989) Cationic liposome-mediated transfection. Focus 11(2):21-25.
Funa, K. et al. (1986) Paucity of .beta..sub.2 -microglobulin expression on small cell lung cancer, bronchial carcinoids and certain other neuroendocrine tumors. Lab Invest. 55:186-193.
Gao, X. et al. (1991) A novel cationic liposome reagent for efficient transfection of mammalian cells. Biochem. Biophys. Res. Commun. 179:280-285.
Gopas, J. et al. (1989) The relationship between MHC antigen expression metastasis. Adv. Cancer Res. 53:89-115.
Gorman, C. et al. (1982) Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol. Cell. Biol. 2:1044-1051.
Gorman, C. et al. (1983) High efficiency DNA-mediated transformation of primate cells. Science 221:551-553.
Gussow, D., et al. (1987) The human .beta..sub.2 -microglobulin gene. Journal of Immunology 139:3132-3138.
Hammerling, G.J. et al. (1986) Manipulation of metastasis and tumour growth by transfection with histocompatibility class I genes. J. Immunogenet. 13:153-157.
Herberman, R.B. (1985) Multiple functions of natural killer cells, including immunoregulation as well as resistance to tumor growth. Concepts Immunopathol. 1:96-132.
Hersh, E., et al. (1994) Phase I study of immunotherapy of malignant melanoma by direct gene transfer. Human Gene Therapy 5:1371-1384.
Holden, C.A. et al. (1983) Absence of human leukocyte antigen molecules in skin tumors and some cutaneous appendages: Evidence using monoclonal antibodies. J. Am. Acad. Dermatol. 9:867-871.
Hosokawa, M. et al. (1983) Alteration of immunogenicity of xenogenized tumor cells in syngeneic rats by the immune responses to virus-associated antigens produced on immunizing cells. Cancer Res. 43:2301-2305.
Hui, K. et al. (1984) Rejection of transplantable AKR leukaemia cells following MHC DNA-mediated cell transformation. Nature 311:750-752.
Invitrogen Molecular Biology Products, San Diego. 1991 Catalog. p. 28, plasmid pRc/RSV.
Isakov, N. et al. (1983) Loss of expression of transplantation antigens encoded by the h-2K locus on Lewis lung carcinoma cells and its relevance to the tumor's metas
Lew Denise
Marquet Magda
Nabel Elizabeth G.
Nabel Gary J.
Hauda Karen M.
Stanton Brian R.
Vical Incorporated
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