Title:
MOBILIZATION OF HEMATOPOIETIC CELLS
Document Type and Number:
WIPO Patent Application WO2005017160
Kind Code:
A3
Abstract:
Improved methods and pharmaceutical compositions are provided herein for mobilizing hematopoietic progenitor cells from bone marrow into peripheral blood, comprising the administration of an effective amount of an inhibitor of GTPases, such as Rac1 and Rac2 alone or in combination. Specifically, methods are disclosed for mobilizing hematopoietic stem cells into a subject's peripheral blood. In particular, embodiments of the method involve inhibition of both Rac1 and Rac2 GTPases to increase the numbers of hematopoietic stem cells into a subject's peripheral blood of a subject. The subject's blood can be processed and used to repopulate the destroyed lymphohematopoietic system of a recipient and may in the future be utilized to repair a variety of non-hematopoietic tissues. Therefore, hematopoietic stem cells mobilized into a subject's peripheral blood by the method of the invention is useful as a source of donor cells in bone marrow transplantation for the treatment of a variety of disorders, including cancer, anemia, autoimmunity and immunodeficiency. They can also be used for increasing white blood cell survival and for chemotherapy.
More Like This:
Inventors:
WILLIAMS DAVID A (US)
ZHENG YI (US)
ZHENG YI (US)
Application Number:
PCT/US2004/026459
Publication Date:
April 21, 2005
Filing Date:
August 12, 2004
Export Citation:
Assignee:
CHILDRENS HOSP MEDICAL CENTER (US)
WILLIAMS DAVID A (US)
ZHENG YI (US)
WILLIAMS DAVID A (US)
ZHENG YI (US)
International Classes:
A61K31/04; A61K31/522; A61K31/7088; A61K35/28; A61K38/19; A61K38/20; C07K14/47; C12N5/0775; A61K35/12; (IPC1-7): A61K38/00; A61K31/04; A61K31/7088; C07K14/47; C12N5/06; C12N15/62
Domestic Patent References:
| WO2003011277A2 | 2003-02-13 | |||
| WO2001078761A2 | 2001-10-25 | |||
| WO2001093900A1 | 2001-12-13 | |||
| WO1999040783A1 | 1999-08-19 |
Foreign References:
| US6117850A | 2000-09-12 | |||
| CA2467557A1 | 2003-05-30 |
Other References:
YANG F -C ET AL: "Rac and Cdc42 GTPases control hematopoietic stem cell shape, adhesion, migration, and mobilization", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 98, no. 10, 8 May 2001 (2001-05-08), pages 5614 - 5618, XP002312312, ISSN: 0027-8424
GU YI ET AL: "Hematopoietic cell regulation by Rac1 and Rac2 guanosine triphosphatases.", SCIENCE, vol. 302, no. 5644, 17 October 2003 (2003-10-17), Washington DC, pages 445 - 449, XP002312006, ISSN: 0036-8075
GAO YUAN ET AL: "Rational design and characterization of a Rac GTPase-specific small molecule inhibitor", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 101, no. 20, 18 May 2004 (2004-05-18), pages 7618 - 7623, XP002312007, ISSN: 0027-8424
WANG LEI ET AL: "A novel strategy for specifically down-regulating individual Rho GTPase activity in tumor cells.", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 278, no. 45, 7 November 2003 (2003-11-07), pages 44617 - 44625, XP002312008, ISSN: 0021-9258
See also references of EP 1656156A2
GU YI ET AL: "Hematopoietic cell regulation by Rac1 and Rac2 guanosine triphosphatases.", SCIENCE, vol. 302, no. 5644, 17 October 2003 (2003-10-17), Washington DC, pages 445 - 449, XP002312006, ISSN: 0036-8075
GAO YUAN ET AL: "Rational design and characterization of a Rac GTPase-specific small molecule inhibitor", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 101, no. 20, 18 May 2004 (2004-05-18), pages 7618 - 7623, XP002312007, ISSN: 0027-8424
WANG LEI ET AL: "A novel strategy for specifically down-regulating individual Rho GTPase activity in tumor cells.", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 278, no. 45, 7 November 2003 (2003-11-07), pages 44617 - 44625, XP002312008, ISSN: 0021-9258
See also references of EP 1656156A2
Download PDF:
Previous Patent: MICROBIAL PRODUCTION OF L-ASCORBIC ACID
Next Patent: CHIMERIC PEPTIDES FOR THE REGULATION OF GTPASES
Next Patent: CHIMERIC PEPTIDES FOR THE REGULATION OF GTPASES