Title:
TRPM-2 ANTISENSE THERAPY
Document Type and Number:
WIPO Patent Application WO2000049937
Kind Code:
A3
Abstract:
It has now been determined that antisense therapy which reduces the expression of TRPM-2 provides therapeutic benefits in the treatment of cancer. In particular, such antisense therapy can be applied in treatment of prostate cancer and renal cell cancer. Addition of antisense TRPM-2 ODN to prostatic tumor cells in vivo is effective for delaying the onset of androgen independence. Thus, prostate cancer can be treated in an individual suffering from prostate cancer by initiating androgen-withdrawal to induce apoptotic cell death of prostatic tumor cells in the individual, and administering to the individual a composition effective to inhibit expression of TRPM-2 by the tumor cells, thereby delaying the progression of prostatic tumor cells to an androgen-independent state in an individual. Combined use of antisense TRPM-2 and taxanes synergistically enhances cytotoxic chemosensitivity of androgen-independent prostate cancer. In addition, it has also been found that antisense TRPM-2 has beneficial effect for other cancer types. Specifically, antisense TRPM-2 ODN enhances chemosensitivity in human Renal cell cancer, a normally chemoresistant disease with no active chemotherapeutic agent having an objective response rate higher than 10 %. Radiation sensitivity is also enhanced when cells expressing TRPM-2 are treated with antisense TRPM-2 ODN. Thus, the antisense TRPM-2 ODNs can be used to enhance hormone sensitivity, chemosensitivity and radiation sensitivity of a variety of cancer types in which expression of TRPM-2 has been observed.
Inventors:
GLEAVE MARTIN (CA)
RENNIE PAUL S (CA)
MIYAKE HIDEAKI (CA)
NELSON COLLEEN (CA)
RENNIE PAUL S (CA)
MIYAKE HIDEAKI (CA)
NELSON COLLEEN (CA)
Application Number:
PCT/US2000/004875
Publication Date:
December 07, 2000
Filing Date:
February 25, 2000
Export Citation:
Assignee:
UNIV BRITISH COLUMBIA (CA)
GLEAVE MARTIN (CA)
RENNIE PAUL S (CA)
MIYAKE HIDEAKI (CA)
NELSON COLLEEN (CA)
GLEAVE MARTIN (CA)
RENNIE PAUL S (CA)
MIYAKE HIDEAKI (CA)
NELSON COLLEEN (CA)
International Classes:
A61K31/00; A61K31/136; A61K31/337; A61K31/66; C12N15/09; A61K31/704; A61K31/7105; A61K38/00; A61K41/00; A61K45/06; A61K48/00; A61P5/24; A61P5/28; A61P35/00; A61P43/00; C07H21/00; C07K14/775; C12N15/113; (IPC1-7): C07H21/04; A61K48/00; C12N15/85; C12Q1/68
Other References:
SENSIBAR ET AL.: "Prevention of cell death induced by tumor necrosis factor alpha in LNCaP cells by overexpression of sulfated glycoprotein-2 (clusterin)", CANCER RESEARCH,, vol. 55, 1 June 1995 (1995-06-01), pages 2431 - 2437, XP002930082
MILNER ET AL.: "Selecting effective antisense reagents on combinatorial oligonucleotide arrays", NATURE BIOTECHNOLOGY,, vol. 15, June 1997 (1997-06-01), pages 537 - 541, XP002930081
BUTTYAN ET AL.: "induction of the TRPM-2 gene in cells undergoing programmed death", MOLECULAR AND CELLULAR BIOLOGY,, vol. 9, no. 8, August 1999 (1999-08-01), pages 3473 - 3481, XP002930080
MILLAR ET AL.: "Localization of mRNAs by in-situ hybridization to the residual body at stages IX-X of the cycle of the rat seminiferous epithelium: fact or artefact?", INTERNATIONAL JOURNAL OF ANDROLOGY,, vol. 17, June 1994 (1994-06-01), pages 149 - 160, XP002930079
DARBY ET AL.: "Vascular expression of clusterin in experimental cyclosporine nephrotoxicity", EXPERIMENTAL NEPHROLOGY,, vol. 3, no. 4, July 1995 (1995-07-01), pages 234 - 239, XP002930078
MILNER ET AL.: "Selecting effective antisense reagents on combinatorial oligonucleotide arrays", NATURE BIOTECHNOLOGY,, vol. 15, June 1997 (1997-06-01), pages 537 - 541, XP002930081
BUTTYAN ET AL.: "induction of the TRPM-2 gene in cells undergoing programmed death", MOLECULAR AND CELLULAR BIOLOGY,, vol. 9, no. 8, August 1999 (1999-08-01), pages 3473 - 3481, XP002930080
MILLAR ET AL.: "Localization of mRNAs by in-situ hybridization to the residual body at stages IX-X of the cycle of the rat seminiferous epithelium: fact or artefact?", INTERNATIONAL JOURNAL OF ANDROLOGY,, vol. 17, June 1994 (1994-06-01), pages 149 - 160, XP002930079
DARBY ET AL.: "Vascular expression of clusterin in experimental cyclosporine nephrotoxicity", EXPERIMENTAL NEPHROLOGY,, vol. 3, no. 4, July 1995 (1995-07-01), pages 234 - 239, XP002930078
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