Gene therapy for solid tumors, papillomas and warts

Details Gene therapy for solid tumors, papillomas and warts Gene therapy for solid tumors, papillomas and warts

1999-09-24

2001-04-17

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

C424S093600, C514S04400A, C435S320100

Reexamination Certificate

active

06217860

ABSTRACT:

BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates generally to the field of gene therapy. More particularly, the present invention relates to a novel gene therapy method of treating solid tumors, papillomas and warts using an adenoviral vector, a combination of adenoviral vectors, other viral vectors, and non-viral DNA transporter systems.
2. Description of the Related Art
Direct introduction of therapeutic genes into malignant cells in vivo can provide an effective treatment of localized tumors. Several novel treatment modalities have recently been attempted. For example, one treatment involves the delivery of normal tumor suppressor genes and/or inhibitors of activated oncogenes into tumor cells. A second treatment involves the enhancement of immunogeneity of tumor cells in vivo by the introduction of cytokine genes. A third treatment involves the introduction of genes that encode enzymes capable of conferring to the tumor cells sensitivity to chemotherapeutic agents. The herpes simplex virus-thymidine kinase (HSV-TK) gene can specifically convert a nucleoside analog (ganciclovir) into a toxic intermediate and cause death in dividing cells. It has recently been reported by Culver et al. (Science 256:1550-1552, 1992) that after delivery of the HSV-TK gene by retroviral transduction, subsequent ganciclovir treatment effectively caused brain tumor regression in laboratory animals. An attractive feature of this treatment modality for localized tumors is the so called “by-stander” effect. In the “by-stander” effect, the HSV-TK expressing tumor cells prevent the growth of adjacent non-transduced tumor cells in the presence of ganciclovir. Thus, not every tumor cell has to express HSV-TK for effective cancer treatment.
The HSV-TK retrovirus used by Culver et al., however, was limited by low viral titer. Thus, effective treatment of brain tumors necessitated the inoculation into animals of virus-producing cells rather than the viral isolate itself. Additionally, in previous experiments with synergeneic rats treated with a retrovirus and ganciclovir, the tumors were necrotic and were invaded by macrophages and lymphocytes. In Example 1, below, athymic mice were used and the tumor cells were destroyed without apparent involvement of the cellular immune response. The prior art remains deficient in the lack of an efficient gene therapy technique for the treatment of solid tumors.
SUMMARY OF THE INVENTION
An object of the present invention is a novel method of gene therapy in humans and animals.
An additional object of the present invention is a method of treating cancer by introducing an adenoviral vector encoding a protein capable of enzymatically converting a prodrug, i.e., a non-toxic compound into a toxic compound, and subsequently administering the prodrug.
A further object of the present invention is to provide a method for combination gene therapy using an adenoviral vector with a “suicide gene”, a protein capable of converting a prodrug; co-administered with a “cytokine gene”, such as the interleukin-2 gene; and subsequently administering the prodrug.
Thus, in accomplishing the foregoing objects there is provided in accordance with one aspect of the present invention a method of treating a solid tumor, papilloma or warts in an animal or human, comprising steps of: introducing an adenoviral vector directly into solid tumor, that vector comprised of the following elements linked sequentially at appropriate distance for functional expression: a promoter, a 5′ mRNA leader sequence, an initiation site, a nucleic acid cassette containing the suicide gene sequence to be expressed, a 3′ untranslated region; and a polyadenylation signal; and administering a prodrug to animal or human, wherein prodrug is converted in vivo in to a toxic compound.
Further, in accomplishing the foregoing objects, there is provided in accordance with one aspect of the present invention a method of treating a solid tumor, papilloma or wart in an animal or human, comprising steps of: introducing an adenoviral vector directly into the solid tumor, that vector comprised of the following elements linked sequentially at appropriate distance for functional expression: a promoter, a 5′ mRNA leader sequence, an initiation site, a nucleic acid cassette containing a suicide gene, a 3′ untranslated region, and a polyadenylation signal; and at the same time introducing a second adenoviral vector, that vector comprised of the following elements linked sequentially at appropriate distance for functional expression: a promoter; a 5′ mRNA leader sequence, an initiation site, a nucleic acid cassette containing a cytokine gene, a 3′ untranslated region, and a polyadenylation signal; and administering a prodrug to animal or human, wherein prodrug is converted in vivo in to a toxic compound.


REFERENCES:
patent: 5631236 (1997-05-01), Woo
patent: 6066624 (2000-05-01), Woo et al.
patent: 0677430 (1997-04-01), None
patent: WO9302556 (1992-07-01), None
patent: WO9310218 (1992-10-01), None
patent: WO9307906 (1992-10-01), None
patent: WO9321959 (1993-05-01), None
patent: WO9428152 (1994-05-01), None
patent: WO9509655 (1994-10-01), None
Manome, Y., et al.; Viral vector transduction of the human deoxycytidine kinase cDNA sensitizes glioma cells to the cytotoxic effects of cytosine arabinoside in vitro and in vivo;Nat. Med.;2(5):567-73 (1996).
Manome, Y., et al.; Gene therapy for malignant gliomas using replication incompetent retroviral and adenoviral vectors encoding the cytochrome P450 2B1 gene together with cyclophosphamide;Gene Ther.;3(6):513-20 (1996).
Lockett, L.J., et al.; Relative efficiency of tumor cell killing in vitro by two enzyme-prodrug systems delivered by identical adenovirus vectors;Clin. Cancer Res.;3(11):2075-80 (1997).
Searle, P.F. et al.; Sensitisation of human ovarian cancer cells to killing by the prodrug CB1954 following retroviral or adenoviral transfer of theE. colinitroreductase gene;Adv. Exp. Med. Biol.;451:107-13 (1998).
Kojima, A. et al.; In vivo human carboxylesterase cDNA gene transfer to activate the prodrug CPT-11 for local treatment of solid tumors;J. Clin. Invest.;101(8):1789-96 (1998).
Chen, S. H. et al.; Combination suicide and cytokine gene therapy for hepatic metastases of colon caracinoma: sustained antitumor immunity prolongs animal survival;Cancer Res.;56(16):3758-62 (1996).
Felzmann, T. et al.; Characterization of the antitumor immune response generated by treatment of murine tumors with recombinant adenoviruses expressing HSVtk, IL-2, IL-6 or B7-1;Gene Ther.;4(12):1322-9 (1997).
Castleden, S.A. et al.; A family of bicistronic vectors to enhance both local and systemic antitumor effects of HSVtk or cytokine expression in a murine melanoma model;Hum. Gene Ther.;8(17):2087-102 (1997).
Cao, X. et al.; Adenovirus-mediated GM-CSF gene and cytosine deaminase gene transfer following by 5-fluorocytosine administration elicit more potent antitumor response in tumor-bearing mice;Gene Ther.;5(8):1130-6 (1998).
Missol-Kolka, E. et al.; Combined therapy of B16(F10) murine melanoma usingE. colicytosine deaminase gene and murine interleukin-4 gene;Neoplasma;45(5):305-11 (1998).
Moriuchi, S. et al.; Enhanced tumor cell killing in the presence of ganciclovir by herpes simplex virus type 1 vector-directed coexpression of human tumor necrosis factor-alpha and herpes simplex virus thymidine kinase;Cancer Res.;58(24):5731-7 (1998).
Oellig, C., et al.; Gene transfer into brain tumor cell lines: reporter gene expression using various cellular and viral promoters; J Neurosci Res; 26:390-396 (1990).
Cheng, L., et al.; In vivo promoter activity and transgene expression in mammalian somatic tissues evaluated by using particle bombardment; Proc. Natl. Acad. Sci. USA; 90:4455-4459 (1993).
Martin-Gallardo, Al, et al.; A comparison of bovine growth-hormone gene expression in mouse L cells directed by Moloney murine-leukemia terminal repeat, simian virus-40 early promoter or cytomegalovirus immediate-early promoter; Gene 70:51-56 (1988).
Pasleau, F., et

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