Title:
COMPOSITIONS AND METHODS FOR PRODUCING HOMOCONJUGATES OF ANTIBODIES WHICH INDUCE GROWTH ARREST OR APOPTOSIS OF TUMOR CELLS
Document Type and Number:
WIPO Patent Application WO1999002567
Kind Code:
A3
Abstract:
This invention discloses monoclonal antibodies (MAbs) which have little or no signaling activity as monomers become potent anti-tumor agents when they are converted into homoconjugates. The homoconjugates exert anti-growth activity by signaling G0/G1 arrest or apoptosis, depending upon which cell surface molecule they bind. This activity is specific and does not require an Fc portion. These conjugates are potent, anti-tumor agents.
Inventors:
GHETIE MARIA-ANA (US)
UHR JONATHAN W (US)
VITETTA ELLEN S (US)
UHR JONATHAN W (US)
VITETTA ELLEN S (US)
Application Number:
PCT/US1998/014222
Publication Date:
April 01, 1999
Filing Date:
July 08, 1998
Export Citation:
Assignee:
UNIV TEXAS (US)
GHETIE MARIA ANA (US)
UHR JONATHAN W (US)
VITETTA ELLEN S (US)
GHETIE MARIA ANA (US)
UHR JONATHAN W (US)
VITETTA ELLEN S (US)
International Classes:
A61K47/48; C07K16/00; C07K16/28; C07K16/32; G01N33/574; A61K38/00; (IPC1-7): C07K16/46; C07K16/30; G01N33/574; A61K39/395
Domestic Patent References:
| WO1991003493A1 | 1991-03-21 | |||
| WO1992004053A1 | 1992-03-19 |
Foreign References:
| EP0453082A1 | 1991-10-23 | |||
| EP0404097A2 | 1990-12-27 | |||
| EP0468637A1 | 1992-01-29 | |||
| US5686072A | 1997-11-11 |
Other References:
M-A. GHETIE ET AL.,: "Anti-CD19 inhibits the growth of human B-cell tumor lines in vitro and of Daudi cells in SCID mice by inducing cell cycle arrest", BLOOD, vol. 83, no. 5, 1994, pages 1329 - 1336, XP002088438
KITA Y ET AL: "ERBB RECEPTOR ACTIVATION, CELL MORPHOLOGY CHANGES, AND APOPTOSIS INDUCED BY ANTI-HER2 MONOCLONAL ANTIBODIES", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 226, no. 1, 4 September 1996 (1996-09-04), pages 59 - 69, XP002027856
WU X ET AL: "APOPTOSIS INDUCED BY AN ANTI-EPIDERMAL GROWTH FACTOR RECEPTOR MONOCLONAl ANTIBODY IN A HUMAN COLORECTAL CARCINOMA CELL LINE AND ITS DELAY BY INSULIN", JOURNAL OF CLINICAL INVESTIGATION, vol. 95, no. 4, April 1995 (1995-04-01), pages 1897 - 1905, XP000645039
M-A. GHETIE ET AL.,: "The use of immunoconjugates in cancer therapy", EXPERT OPINION ON INVESTIGATIONAL DRUGS, vol. 5, no. 3, 1996, pages 309 - 321, XP002088439
E.S. VITETTA AND J.W. UHR: "Monoclonal antibodies as agonists: an expanded role for their use in cancer therapy", CANCER RESEARCH, vol. 54, 1994, pages 5301 - 5309, XP002088440
R. MARCHES ET AL.,: "Tumor dormancy and cell signalling - III: role of hypercrosslinking of IgM and CD40 on the induction of cell cycle arrest and apoptosis in B lymphoma cells", THERAPEUTIC IMMUNOLOGY, vol. 2, no. 3, 1995, pages 125 - 136, XP002088441
E. RACILA ET AL.,: "Tumor dormancy and cell signalling: Anti-mu-induced apoptosis in human B-lymphoma cells is not caused by an APO-1-APO-1 ligand interaction", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, vol. 93, 1996, WASHINGTON DC, US, pages 2165 - 2168, XP002088442
KITA Y ET AL: "ERBB RECEPTOR ACTIVATION, CELL MORPHOLOGY CHANGES, AND APOPTOSIS INDUCED BY ANTI-HER2 MONOCLONAL ANTIBODIES", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 226, no. 1, 4 September 1996 (1996-09-04), pages 59 - 69, XP002027856
WU X ET AL: "APOPTOSIS INDUCED BY AN ANTI-EPIDERMAL GROWTH FACTOR RECEPTOR MONOCLONAl ANTIBODY IN A HUMAN COLORECTAL CARCINOMA CELL LINE AND ITS DELAY BY INSULIN", JOURNAL OF CLINICAL INVESTIGATION, vol. 95, no. 4, April 1995 (1995-04-01), pages 1897 - 1905, XP000645039
M-A. GHETIE ET AL.,: "The use of immunoconjugates in cancer therapy", EXPERT OPINION ON INVESTIGATIONAL DRUGS, vol. 5, no. 3, 1996, pages 309 - 321, XP002088439
E.S. VITETTA AND J.W. UHR: "Monoclonal antibodies as agonists: an expanded role for their use in cancer therapy", CANCER RESEARCH, vol. 54, 1994, pages 5301 - 5309, XP002088440
R. MARCHES ET AL.,: "Tumor dormancy and cell signalling - III: role of hypercrosslinking of IgM and CD40 on the induction of cell cycle arrest and apoptosis in B lymphoma cells", THERAPEUTIC IMMUNOLOGY, vol. 2, no. 3, 1995, pages 125 - 136, XP002088441
E. RACILA ET AL.,: "Tumor dormancy and cell signalling: Anti-mu-induced apoptosis in human B-lymphoma cells is not caused by an APO-1-APO-1 ligand interaction", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, vol. 93, 1996, WASHINGTON DC, US, pages 2165 - 2168, XP002088442
Download PDF: