Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1996-02-15
2000-05-23
Crouch, Deborah
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
424 932, A61K 4800
Patent
active
060666242
DESCRIPTION:
BRIEF SUMMARY
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 destoyed 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 adeno
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Chen Shu-Hsia
Woo Savio L. C.
Baylor College of Medicine
Crouch Deborah
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