In vivo transfer of the HSV-TK gene implanted retroviral produce

Details In vivo transfer of the HSV-TK gene implanted retroviral produce In vivo transfer of the HSV-TK gene implanted retroviral produce

1991-08-13

1996-06-25

Stone, Jacqueline M.

Drug, bio-affecting and body treating compositions

Whole live micro-organism, cell, or virus containing

Genetically modified micro-organism, cell, or virus

424 932, 424 936, 514 44, A01N 6300, A01N 4304, A61K 4800, A61K 3170

Patent

active

055297749

ABSTRACT:
The present invention is directed to methods of transferring therapeutic genes to brain tumor cells in order to kill the cells. In general, the method of the present invention comprises: (1) introducing a retrovirus containing a selectable marker and at least one gene required for its replication into producer cells such that integration of the proviral DNA corresponding to the retrovirus into the genome of the producer cell results in the generation of a modified retrovirus wherein at least one of the genes required for replication of the retrovirus is replaced by the therapeutic gene or genes; (2) selecting producer cells in which the modified retrovirus is incorporated as part of the genome of the producer cells; (3) grafting the producer cells in proximity to the dividing tumor cell in order to infect the tumor cell with the modified retrovirus, thereby transferring the therapeutic gene or genes to the tumor cell; and (4) killing the cells by administering a substance that is metabolized by the therapeutic gene transferred to the tumor cells into a metabolite that kills the cells. Suitable retroviral vectors and methods for generating them, producer cells, and grafting methods are described.

REFERENCES:
patent: 4083960 (1979-04-01), Yamashita et al.
Moolten et al (1990) J. Natl. Cancer Inst. 82, 297-300.
Shimohama et al(1989) Molic. Brain Res. 5, 271-278.
Culven et al (1992) Science 256, 1550-1552.
Ram et al (1993) Cancer Res. 53, 83-88.
Barba et al (1994) Proced. Natl. Acad. Sci 91, 4348-4352.
Ezzeddine et al (1991) The New Biologist 3, 608-614.
Kimler (1994) J. Neuro-Oncology 20, 103-109.
Oldfield et al (1993) Human Gene Therapy 4, 39-69.
Comprehensive Textbook of Oncology, Moossa et al eds, Williamsa Wilkins, Baltimore, 1991, pp. 477-485 and 537-556.
Rosenstein, "Neocortical Transplants in the Mammalian Brian lack a Bloood-brain Barrier to Macromolecules", Science 235: 772-774 (1987).
Anderson, "Prospects for Human Gene Therapy", Science 226:401-409 (1984).
Friedmann et al., "Gene Therapy for Human Genetic Disease?", Science 175:949-955 (1972).
Friedmann, Gene Therapy Fact and Fiction , Cold Spring Harbor Laboratory, New York (1983).
Rosenberg et al., "A New Approach to the Adoptive Immunotheraphy of Cancer with Tumor-Infiltrating Lymphocytes", Science 242:1575-1578 (1988).
Wolff et al., "Grafting Fibroblasts Genetically Modified to Produce L-dopa in a Rat Model of Parkinson Disease", Proc. Natl. Acad. Sci. USA 86:9011-9014 (1989) 1.
Moolten & Wells, "Curability of tumors Bearing Herpes Thymidine kinase Genes Transferred by Retroviral Vectors", J. Natl. Cancer Inst. 82:297-300 (1990).
Moolten, "Tumor Chemosensitivity Conferred by Inserted Herpes Thymidine Kinase Genes: Paradigm for a Prospective Cancer Control Strategy", Cancer Res. 46:527-581 (1986).
Gage et al., "Implantation of Genetically Engineered Cells to the Brain", Ch. 86, Progress in Brain Research, vol. 78, pp. 651-658 (1988).
Yee et al., "Gene Expression from a Transcriptionally Disabled Retroviral Vector", Cold Spring Harbor Symp. on Quant. Biol. vol. LI, pp. 1021-1026 (1986).
Wolff et al., "Expression of Retrovirally Transduced Genes in Primary Cultures of Adult Rat Hepatocytes", Proc. Natl. Acad. Sci. USA 84: 3344-3348 (1987).
Jolly et al., "High-Efficiency Gene Transfer into Cells". Meth. in Enzymol. 149:10-25 (1987).
Miller et al., "Generation of Helper-Free Amphotropic Retroviruses that Transduce a Dominant-Acting, Methotrexate-Resistant Dihydrofolate Reductase Gene", Mol. Cell. Biol. 5:431-437 (1985).
Eglitis et al., "Retroviral Vectors for Introduction of Genes into Mammalian Cells", Biotechniques 6:608-614 (1988).
Bender et al., "Evidence that the Packaging Signal of Moloney Murine Leukemia Virus Extends into the gag Region", J. Virol. 61:1639-1646 (1987).
Howell et al., "Gene Therapy for Thioguanine-Resistant Human Leukemia", Mol. Biol. Med. 4:157-168 (1987).
Moolten & Brodeur, Proc. Am. Assoc. Cancer Res. 29:461 (1988).
Das, "Intraparenchymal Transplantation", Neural Grafting in the Mammalian CNS, Bjorklund and Stenevi, eds., Ch. 3, pp. 23-30 (1985).
Freed, "Transplantation of Tissues to the Cerebral Ventricles: methodological Details and Rate of Graft Survival", Neural Grafting in the Mammalian CNS, Bjorklund and Stenevi, eds., Ch. 4, pp. 31-40 (1985).
Brundin et al., "Intracerebral Grafts of neuronal Cell Suspensions", Neural Grafting in the Mammalian CNS, Bjorklund and Stenevi, eds., Ch. 6, pp. 51-60 (1985).
David et al., "Peripheral Nerve Transplantation Techniques to Study Axonal Regeneration from the CNS of Adult Mammals,"Neural Grafting in the Mammalian CNS, Bjorklund and Stenevi, eds., Ch. 7, pp. 61-70 (1985).
Seiger, "Preparation of Immature Central Nervous System Regions for Transplantation", Neural Grafting in the Mammalian CNS, Bjorklund and Stenevi, eds., Ch. 8, pp. 71-77 (1985).
Mann et al., "Construction of a Retrovirus Packaging Mutant and its Use to Produce Helper-Free Defective Retrovirus", Cell 33:153-159 (1983).
Shimohama et al., "Grafting Genetically Modified Cells into the Rat Brain: Characterises of E. coli .beta.-Galactosidase as a Reporter Gene", Mol. Brain Res. 5:271-278 (1989).

Affiliated with

Also associated with

Rating

In vivo transfer of the HSV-TK gene implanted retroviral produce does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with In vivo transfer of the HSV-TK gene implanted retroviral produce, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and In vivo transfer of the HSV-TK gene implanted retroviral produce will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2187148