Cyclosphosphamide in combination with anti-idiotypic vaccines 机翻标题: 暂无翻译,请尝试点击翻译按钮。

公开号/公开日
WO2008034074 A2 2008-03-20 [WO200834074]WO2008034074 A3 2009-01-29 [WO200834074] / 2008-03-202009-01-29
申请号/申请日
2007WO-US78521 / 2007-09-14
发明人
BRODSKY ROBERT;JONES RICHARD J;O'DONNELL FRANK;BONITZ SUSAN;SANTOS CARLOS;
申请人
ACCENTIA BIOPHARMACEUTICALS;JOHNS HOPKINS UNIVERSITY;
主分类号
IPC分类号
A01N-061/00
摘要
(WO200834074) The present invention relates to methods of treating a cancer and in particular, a B- cell derived cancer, using a lymphocytotoxic but hematopoeitic cell sparing high-dose pulsed amount of an oxazaphosphorine drug in combination with immune therapeutics such as, for example, an autologous idiotypic vaccine and monoclonal antibodies that selectively bind B-cell specific antigens.
机翻摘要
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地址
代理人
代理机构
;
优先权号
2006US-60844830 2006-09-15
主权利要求
(WO200834074) Claims 1. A method for eliminating or substantially reducing non-Hodgkin's lymphoma in a subject comprising administering a lymphocytotoxic but hematopoeitic stem cell sparing high-dose pulsed amount of an oxazaphosphorine drug to the subject, such that the subject's immune system reconstitutes without stem cell transplantation, and administering an effective amount of an autologous anti-idiotypic vaccine, thereby to eliminate or substantially reduce non-Hodgkin's lymphoma in the subject. 2. A method for eliminating or substantially reducing Hodgkin's disease in a subject comprising administering a lymphocytotoxic but hematopoeitic stem cell sparing high-dose pulsed amount of an oxazaphosphorine drug to the subject, such that the subject's immune system reconstitutes without stem cell transplantation, and administering an effective amount of an autologous anti-idiotypic vaccine, thereby to eliminate or substantially reduce Hodgkin's lymphoma in the subject. 3. A method for eliminating or substantially reducing chronic lymphocytic leukemia in a subject comprising administering a lymphocytotoxic but hematopoeitic stem cell sparing high-dose pulsed amount of an oxazaphosphorine drug to the subject, such that the subject's immune system reconstitutes without stem cell transplantation, and administering an effective amount of an autologous anti-idiotypic vaccine, thereby to eliminate or substantially reduce chronic lymphocytic leukemia in the subject. 4. A method for eliminating or substantially reducing multiple myeloma in a subject comprising administering a lymphocytotoxic but hematopoeitic stem cell sparing high-dose pulsed amount of an oxazaphosphorine drug to the subject, such that the subject's immune system reconstitutes without stem cell transplantation, and administering an effective amount of an autologous anti-idiotypic vaccine, thereby to eliminate or substantially reduce multiple myeloma in the subject. 5. A method for eliminating or substantially reducing mantle cell lymphoma in a subject comprising administering a lymphocytotoxic but hematopoeitic stem cell sparing high-dose pulsed amount of an oxazaphosphorine drug to the subject, such that the subject's immune system reconstitutes without stem cell transplantation, and administering an effective amount of an autologous anti-idiotypic vaccine, thereby to eliminate or substantially reduce mantle cell lymphoma in the subject. 6. A method of any one of claims 1-5, further comprising administering a monoclonal antibody that selectively binds a B-cell specific antigen. 7. The method of claims 1-5, wherein the autologous anti-idiotypic vaccine is administered in conjunction with an effective amount of granulocyte-monocyte colony stimulating factor. 8. The method of claim 6, wherein the B-cell specific antigen is selected from the group consisting of CD3d, CD5, CD6, CD9, CD19, CD20, CD21, CD22, CD23, CD24, CD27, CD28, CD37, CD38, CD40, CD45, CD46, CD48, CD53, CD69, CD70, CD72, CD73, CD79a, CD79b, CD80, CD81, CD83, CD85a, CD85d, CD85e, CD85h, CD85i, CD85j, CD85k, CD86, CD96, CD98, CDlOO, CD121b, CD124, CD127, CD132, CD150, CD152, CD154, CD157, CD166, CD169, CD 179a, CD 179b, CDl 80, CDl 85, CD 196, CD 197, CD205, CDw210a, CD213al, CD257, CD267, CD268, CD269, CD274, CD275, CD276, CD278, CD279, CD300a, CD300c, CD307, CD314, CD316, CD317, CD319, CD320, CDw327, and CD331. 9. The method of claim 6, wherein the monoclonal antibody selectively binds CD-20. 10. The method of claim 6, wherein the monoclonal antibody selectively binds CD-22. 11. The method of any one of claims 1 -5, wherein the lymphocytotoxic but hematopoeitic stem cell sparing high-dose pulsed amount of an oxazaphosphorine drug is 50 mg/kg/day. 12. The method of any one of claims 1-5, wherein the lymphocytotoxic but hematopoeitic stem cell sparing high-dose pulsed amount of an oxazaphosphorine drug is administered to the subject for 4 days. 13. The method of any one of claims 1-5, wherein the lymphocytotoxic but hematopoeitic stem cell sparing high-dose pulsed amount of an oxazaphosphorine drug is 50 mg/kg/day administered for 4 days. 14. The method of any one of claims 1-5, wherein the oxazaphosphorine drug is cyclophosphamide administered in the amount of 50 mg/Kg for 4 days. 15. The method of any one of claims 1-5, wherein the oxazaphosphorine drug is powdered cyclophosphamide or a pharmaceutically acceptable salt, solvate, prodrug, or metabolite thereof. 16. The method of any one of claims 1-5, wherein the oxazaphosphorine drug is lyophilized cyclophosphamide or a pharmaceutically acceptable salt, solvate, prodrug, or metabolite thereof. 17. A method of eliminating or substantially reducing a B-cell derived cancer selected from the group consisting of non-Hodgkin's lymphoma, Hodgkin's lymphoma, mantle cell lymphoma, chronic lymphocytic leukemia and multiple myeloma in a subject comprising administering (a) a lymphocytotoxic but hematopoeitic stem cell sparing high-dose pulsed amount of an oxazaphosphorine drug to the subject; and (b) administering an effective amount of an autologous anti-idiotypic vaccine, thereby to eliminate or substantially reduce the B-cell derived cancer in the subject. 18. The method of claim 17, further comprising administering an effective amount of a monoclonal antibody that selectively binds a B-cell specific antigen. 19. The method of claim 17, wherein the autologous anti-idiotypic vaccine is administered in conjunction with an effective amount of GM-CSF. 20. A method of eliminating or substantially reducing a B-cell derived cancer selected from the group consisting of non-Hodgkin's lymphoma, Hodgkin's lymphoma, mantle cell lymphoma, chronic lymphocytic leukemia and multiple myeloma in a subject comprising administering to the subject: (a) a lymphocytotoxic but hematopoeitic stem cell sparing high-dose pulsed amount of an oxazaphosphorine drug; (b) an effective amount of an autologous anti-idiotypic vaccine in conjunction with an effective amount of GM-CSF; and (c) an effective amount of one or more monoclonal antibodies that selectively bind one or more B-cell specific antigens, thereby to eliminate or substantially reduce the B-cell derived cancer in the subject. 21. The method of claim 20, wherein the lymphocytotoxic but hematopoeitic stem cell sparing high-dose pulsed amount of an oxazaphosphorine drug is 50 mg/Kg of cyclophosphamide administered daily for 4 days. 22. The method of claim 20, wherein one or more monoclonal antibodies are selected from antibodies that selectively bind CD3d, CD5, CD6, CD9, CD19, CD20, CD21, CD22, CD23, CD24, CD27, CD28, CD37, CD38, CD40, CD45, CD46, CD48, CD53, CD69, CD70, CD72, CD73, CD79a, CD79b, CD80, CD81, CD83, CD85a, CD85d, CD85e, CD85h, CD85i, CD85J, CD85k, CD86, CD96, CD98, CDlOO, CD121b, CD124, CD127, CD132, CD150, CD152, CD154, CD157, CD 166, CD 169, CD 179a, CD 179b, CDl 80, CDl 85, CD 196, CD 197, CD205, CDw210a, CD213al, CD257, CD267, CD268, CD269, CD274, CD275, CD276, CD278, CD279, CD300a, CD300c, CD307, CD314, CD316, CD317, CD319, CD320, CDw327, or CD331. 23. The method of claim 20, wherein the autologous anti-idiotypic vaccine generates an immune response against a B-cell derived cancer specific antigen. 24. The method of any one of claims 1-5, further comprising administering an effective amount of Mesna.
法律状态
(WO200834074) LEGAL DETAILS FOR WO2008034074  Actual or expected expiration date=2010-03-15    Legal state=DEAD    Status=LAPSED     Event publication date=2007-09-14  Event code=WO/APP  Event indicator=Pos  Event type=Examination events  Application details  Application country=WO WOUS2007078521  Application date=2007-09-14  Standardized application number=2007WO-US78521     Event publication date=2008-03-20  Event code=WO/A2  Event type=Examination events  International application published without international search report  Publication country=WO  Publication number=WO2008034074  Publication stage Code=A2  Publication date=2008-03-20  Standardized publication number=WO200834074     Event publication date=2009-01-29  Event code=WO/A3  Event indicator=Pos  Event type=Examination events  Later publication of ISR with revised front page  Publication country=WO  Publication number=WO2008034074  Publication stage Code=A3  Publication date=2009-01-29  Standardized publication number=WO200834074     Event publication date=2010-03-15  Event code=WO/EETL  Event type=Event indicating Not In Force  PCT Application validity period expired. LEGAL DETAILS FOR DESIGNATED STATE DE  Actual or expected expiration date=2009-03-17    Legal state=DEAD    Status=LAPSED   Corresponding cc:  Designated or member state=DE     Event publication date=2009-03-17  Event code=WO/NENP  Event type=Event indicating Not In Force  Non-entry into the national phase in: Corresponding cc:  Designated or member state=DE
专利类型码
A2A3
国别省市代码
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