Title:
TREATMENT OF CHRONIC INFLAMMATORY DISEASE BY INHIBITING SUB-GROUPS OF ACTIVATED T-CELLS
Document Type and Number:
WIPO Patent Application WO2001021202
Kind Code:
A3
Abstract:
The invention provides a method of treatment of a chronic inflammatory disease (such as rheumatoid arthritis) in a patient, the method comprising the administration to the patient of a compound that selectively inhibits Tck cells. Preferably, said compound selectively inhibits Tck cell-induced release of one or more pro-inflammatory cytokines from monocytes. Advantageously, said compound inhibits NF- kappa B. Conveniently, said compound activates PI3 kinase. The invention further provides a method of identifying a compound with efficacy in the treatment of a chronic inflammatory disease comprising the step of testing said compound for an ability to selectively inhibit Tck cells. Preferably, said method of identifying a compound with efficacy in the treatment of a chronic inflammatory disease comprises the step of testing said compound for an ability to selectively inhibit Tck cell-induced release of one or more pro-inflammatory cytokines from monocytes. Conveniently, the pro-inflammatory cytokine is tumour necrosis factor alpha (TNF alpha ). The invention further provides compounds identifiable or identified by said methods and the use of said compounds in medicine. Additionally, the invention provides an antibody-like molecule with specificity for Tck cells, and compounds comprising said antibody-like molecule and a cytotoxic moiety.
Inventors:
BRENNAN FIONULA MARY (GB)
FELDMANN MARC (GB)
FOXWELL BRIAN MAURICE JOHN (GB)
FELDMANN MARC (GB)
FOXWELL BRIAN MAURICE JOHN (GB)
Application Number:
PCT/GB2000/003660
Publication Date:
October 11, 2001
Filing Date:
September 25, 2000
Export Citation:
Assignee:
KENNEDY RHEUMATOLOGY INST (GB)
BRENNAN FIONULA MARY (GB)
FELDMANN MARC (GB)
FOXWELL BRIAN MAURICE JOHN (GB)
BRENNAN FIONULA MARY (GB)
FELDMANN MARC (GB)
FOXWELL BRIAN MAURICE JOHN (GB)
International Classes:
G01N33/50; A61K35/14; A61K38/00; A61K38/17; A61K39/395; A61K45/00; A61K48/00; A61P1/04; A61P9/10; A61P19/02; A61P25/00; A61P29/00; A61P37/06; C07K16/28; C07K19/00; C12N1/15; C12N1/19; C12N1/21; C12N5/10; C12N15/09; C12P21/08; C12Q1/02; C12Q1/68; G01N27/447; G01N33/15; A61K39/00; (IPC1-7): C12N15/13; C12N15/62; C12N15/06; G01N33/53; G01N33/573; C12Q1/68; C12Q1/37; C07K16/28; A61K38/48; C12N5/12; A61K47/48
Foreign References:
| US5085985A | 1992-02-04 | |||
| EP0896999A1 | 1999-02-17 |
Other References:
FOXWELL BRIAN ET AL: "Efficient adenoviral infection with IkappaBalpha reveals that macrophage tumor necrosis factor alpha production in rheumatoid arthritis is NF-kappaB dependent.", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES, vol. 95, no. 14, 7 July 1998 (1998-07-07), July 7, 1998, pages 8211 - 8215, XP002098099, ISSN: 0027-8424
EIGLER A ET AL: "Taming TNF: strategies to restrain this proinflammatory cytokine", IMMUNOLOGY TODAY,GB,ELSEVIER PUBLICATIONS, CAMBRIDGE, vol. 18, no. 10, 1 October 1997 (1997-10-01), pages 487 - 492, XP004091986, ISSN: 0167-5699
SEBBAG M ET AL: "Cytokine stimulation of T lymphocytes regulates their capacity to induce monocyte production of tumor necrosis factor-alpha, but not interleukin-10: possible relevance to pathophysiology of rheumatoid arthritis.", EUROPEAN JOURNAL OF IMMUNOLOGY, (1997 MAR) 27 (3) 624-32., XP000971524
WARD S G ET AL: "PI 3-kinase: a pivotal pathway in T-cell activation?", IMMUNOLOGY TODAY,GB,ELSEVIER PUBLICATIONS, CAMBRIDGE, vol. 17, no. 4, 1 April 1996 (1996-04-01), pages 187 - 197, XP004034692, ISSN: 0167-5699
BHATTACHARYYA S P ET AL: "Activated T lymphocytes induce degranulation and cytokine production by human mast cells following cell-to-cell contact.", JOURNAL OF LEUKOCYTE BIOLOGY, (1998 MAR) 63 (3) 337-41., XP000971545
CHABOT S ET AL: "Microglial production of TNF - alpha is induced by activated T lymphocytes. Involvement of VLA-4 and inhibition by interferonbeta-1b.", JOURNAL OF CLINICAL INVESTIGATION, (1997 AUG 1) 100 (3) 604-12., XP000971530
AVICE M N ET AL: "Lymphocyte activation gene-3, a MHC class II ligand expressed on activated T cells, stimulates TNF - alpha and IL-12 production by monocytes and dendritic cells.", JOURNAL OF IMMUNOLOGY, (1999 MAR 1) 162 (5) 2748-53., XP002156054
MACLEAN J A ET AL: "Anti -CD3: anti - IL - 2 receptor bispecific monoclonal antibody. Targeting of activated T cells in vitro.", JOURNAL OF IMMUNOLOGY, (1993 FEB 15) 150 (4) 1619-28., XP002156055
LONDEI M ET AL: "Cloning of activated t cells from rheumatoid arthritis joints detection of collagen type ii specific cells.", SYMPOSIUM ON MOLECULAR AND CELLULAR MECHANISMS OF HUMAN HYPERSENSITIVITY AND AUTOIMMUNITY HELD AT THE 17TH ANNUAL UCLA (UNIVERSITY OF CALIFORNIA-LOS ANGELES) SYMPOSIA ON MOLECULAR AND CELLULAR BIOLOGY, KEYSTONE, COLORADO, USA, APRIL 17-23, 1988. J CE, XP000971527
COHEN S B ET AL: "High level of interleukin-10 production by the activated T cell population within the rheumatoid synovial membrane.", ARTHRITIS AND RHEUMATISM, (1995 JUL) 38 (7) 946-52., XP000971529
MCINNES I B ET AL: "Interleukin 15: a proinflammatory role in rheumatoid arthritis synovitis", IMMUNOLOGY TODAY,GB,ELSEVIER PUBLICATIONS, CAMBRIDGE, vol. 19, no. 2, 1 February 1998 (1998-02-01), pages 75 - 79, XP004107030, ISSN: 0167-5699
EIGLER A ET AL: "Taming TNF: strategies to restrain this proinflammatory cytokine", IMMUNOLOGY TODAY,GB,ELSEVIER PUBLICATIONS, CAMBRIDGE, vol. 18, no. 10, 1 October 1997 (1997-10-01), pages 487 - 492, XP004091986, ISSN: 0167-5699
SEBBAG M ET AL: "Cytokine stimulation of T lymphocytes regulates their capacity to induce monocyte production of tumor necrosis factor-alpha, but not interleukin-10: possible relevance to pathophysiology of rheumatoid arthritis.", EUROPEAN JOURNAL OF IMMUNOLOGY, (1997 MAR) 27 (3) 624-32., XP000971524
WARD S G ET AL: "PI 3-kinase: a pivotal pathway in T-cell activation?", IMMUNOLOGY TODAY,GB,ELSEVIER PUBLICATIONS, CAMBRIDGE, vol. 17, no. 4, 1 April 1996 (1996-04-01), pages 187 - 197, XP004034692, ISSN: 0167-5699
BHATTACHARYYA S P ET AL: "Activated T lymphocytes induce degranulation and cytokine production by human mast cells following cell-to-cell contact.", JOURNAL OF LEUKOCYTE BIOLOGY, (1998 MAR) 63 (3) 337-41., XP000971545
CHABOT S ET AL: "Microglial production of TNF - alpha is induced by activated T lymphocytes. Involvement of VLA-4 and inhibition by interferonbeta-1b.", JOURNAL OF CLINICAL INVESTIGATION, (1997 AUG 1) 100 (3) 604-12., XP000971530
AVICE M N ET AL: "Lymphocyte activation gene-3, a MHC class II ligand expressed on activated T cells, stimulates TNF - alpha and IL-12 production by monocytes and dendritic cells.", JOURNAL OF IMMUNOLOGY, (1999 MAR 1) 162 (5) 2748-53., XP002156054
MACLEAN J A ET AL: "Anti -CD3: anti - IL - 2 receptor bispecific monoclonal antibody. Targeting of activated T cells in vitro.", JOURNAL OF IMMUNOLOGY, (1993 FEB 15) 150 (4) 1619-28., XP002156055
LONDEI M ET AL: "Cloning of activated t cells from rheumatoid arthritis joints detection of collagen type ii specific cells.", SYMPOSIUM ON MOLECULAR AND CELLULAR MECHANISMS OF HUMAN HYPERSENSITIVITY AND AUTOIMMUNITY HELD AT THE 17TH ANNUAL UCLA (UNIVERSITY OF CALIFORNIA-LOS ANGELES) SYMPOSIA ON MOLECULAR AND CELLULAR BIOLOGY, KEYSTONE, COLORADO, USA, APRIL 17-23, 1988. J CE, XP000971527
COHEN S B ET AL: "High level of interleukin-10 production by the activated T cell population within the rheumatoid synovial membrane.", ARTHRITIS AND RHEUMATISM, (1995 JUL) 38 (7) 946-52., XP000971529
MCINNES I B ET AL: "Interleukin 15: a proinflammatory role in rheumatoid arthritis synovitis", IMMUNOLOGY TODAY,GB,ELSEVIER PUBLICATIONS, CAMBRIDGE, vol. 19, no. 2, 1 February 1998 (1998-02-01), pages 75 - 79, XP004107030, ISSN: 0167-5699
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