Title:
IMPROVEMENTS RELATING TO CANCER THERAPY
Document Type and Number:
WIPO Patent Application WO1995012678
Kind Code:
A3
Abstract:
PCT No. PCT/GB94/02423 Sec. 371 Date Jul. 1, 1996 Sec. 102(e) Date Jul. 1, 1996 PCT Filed Nov. 4, 1994 PCT Pub. No. WO95/12678 PCT Pub. Date May 11, 1995A system is disclosed which comprises: (i) a viral vector comprising a nucleotide sequence encoding a nitroreductase, which nitroreductase is capable of converting a prodrug into a cytotoxic drug; and (ii) a prodrug capable of being converted into a cytotoxic drug by the nitroreductase encoded by the vector. The disclosed invention also includes methods for killing cancerous and/or non-cancerous cells using the system described above. Included in the invention are methods for killing cells in vitro by introducing a vector encoding a nitroreductase into the cells, and then by providing a prodrug to the cells growing in vitro. Also included are methods in which cancerous and/or non-cancerous cells are killed in vivo in an animal or human by administering the vector and prodrug directly to cells of the animal or human. The invention further includes methods in which cancerous and/or non-cancerous cells are killed in vivo in an animal or human, by introducing a viral vector encoding a nitroreductase into animal or human cells growing in vitro so that the nitroreductase is produced in the cells, administering the cells to an animal or human subject, and then administering a prodrug to the animal or human, where it is converted into a cytotoxic agent in nitroreductase-containing cells of the animal or human.
Inventors:
CONNORS THOMAS (GB)
KNOX RICHARD (GB)
SHERWOOD ROGER (GB)
KNOX RICHARD (GB)
SHERWOOD ROGER (GB)
Application Number:
PCT/GB1994/002423
Publication Date:
June 15, 1995
Filing Date:
November 04, 1994
Export Citation:
Assignee:
CANCER RES CAMPAIGN TECH (GB)
CONNORS THOMAS (GB)
KNOX RICHARD (GB)
SHERWOOD ROGER (GB)
CONNORS THOMAS (GB)
KNOX RICHARD (GB)
SHERWOOD ROGER (GB)
International Classes:
A61K31/265; A61K31/27; A61K31/40; C12N15/00; A61K35/76; A61K38/00; A61K38/44; A61K45/00; A61K48/00; A61P35/00; A61P43/00; C07H21/04; C07K14/195; C12N9/02; C12N15/53; (IPC1-7): C12N15/53; C12N15/86; A61K48/00
Foreign References:
| EP0330432A1 | 1989-08-30 | |||
| EP0540263A1 | 1993-05-05 |
Other References:
ANLEZARK, G.M. ET AL.: "The bioactivation of 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954)--I. Purification and properties of a nitroreductase enzyme from Escherichia coli -- a potential enzyme for antibody-directed enzyme prodrug therapy (ADEPT)", BIOCHEM.PHARMACOL., vol. 44, no. 12, 15 December 1992 (1992-12-15), ENGLAND, pages 2289 - 2295
HUBER, B.E. ET AL.: "Retroviral-mediated gene therapy for the treatment of hepatocellular carcinoma: An innovative approach for cancer therapy", PROC.NATL.ACAD.SCI., vol. 88, September 1991 (1991-09-01), USA, pages 8039 - 8043
MULLEN, C.A. ET AL.: "Transfer of the bacterial gene for cytosine deaminase to mammalian cells confers lethal sensitivity to 5-fluorocytosine: a negative selection system", PROC.NATL.ACAD.SCI., vol. 89, 1992, USA, pages 33 - 37
HUBER, B.E. ET AL.: "Retroviral-mediated gene therapy for the treatment of hepatocellular carcinoma: An innovative approach for cancer therapy", PROC.NATL.ACAD.SCI., vol. 88, September 1991 (1991-09-01), USA, pages 8039 - 8043
MULLEN, C.A. ET AL.: "Transfer of the bacterial gene for cytosine deaminase to mammalian cells confers lethal sensitivity to 5-fluorocytosine: a negative selection system", PROC.NATL.ACAD.SCI., vol. 89, 1992, USA, pages 33 - 37
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