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Combination therapy

An inhibitor, effective dose technology, applied in the field of therapy and medical chemistry, can solve the problem of low effect of leukemia

Inactive Publication Date: 2009-07-29
GENZYME CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Specifically, chemotherapy or radiation therapy for leukemia may be less effective if leukemia or pre-leukemic cells are maintained or attracted to the bone marrow rather than in circulation where it is easier to treat them

Method used

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  • Combination therapy
  • Combination therapy
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Experimental program
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Effect test

Embodiment 1

[0090] Compounds can be administered intravenously as a single agent or as a combination at doses of 1 mg / kg (15057) and 2 mg / kg (3100). AMD15057 (VLA-4 inhibitor) was formulated at a concentration of 0.2 mg / ml and AMD3100 was formulated at a concentration of 0.4 mg / ml. The vehicle was 36:45:10 PG / water / ethanol, pH 6.6. Blood samples are collected at appropriate intervals for assays including white blood cell counts and progenitor cell levels by colony formation assays.

Embodiment 2

[0092] transfer leukemia cells

[0093] A mouse model of human acute promyelocytic leukemia (APL) was used in which the PML-RARa transgene was knocked into one allele of the murine cathepsin G locus. To track leukemia cells more efficiently, banked APL tumors were transduced with a bifunctional reporter gene encoding a fusion protein containing click beetle red (CBR) luciferase, a bioluminescent Imaging (BLI) optical reporter) and EGFP for ex vivo cell sorting (CBR / EGFP). Use MoFlo TM Cell sorter isolation of EGFP+ cells yields large numbers of CBR / EGFP+ APL cells, which are passaged in secondary syngeneic recipients. Following intravenous or intraperitoneal injection of these cells, cells displaying the APL phenotype (CD34 / GR1 co-expression) and displaying luciferase activity, secondary recipients developed rapidly fatal acute leukemia. The rapid transfer of CBR / EGFP+ APL cells to the bone marrow (BM) microenvironment following intravenous injection into syngeneic recipi...

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Abstract

Methods to mobilize progenitor and / or stem cells from the bone marrow to the bloodstream by administering a combination of at least one CXCR4 inhibitor and at least one VLA-4 inhibitor are described. The combinations may also be used to treat multiple myeloma.

Description

[0001] related application [0002] This application claims priority to US Provisional Application Serial No. 60 / 835,290, filed August 2, 2006, which is hereby incorporated by reference in its entirety. technical field [0003] This invention is in the field of therapeutic and medicinal chemistry. In particular, the present invention relates to methods of rapidly mobilizing progenitor / stem cells, including precancerous progenitor cells and / or stem cells, into the bloodstream using combination therapy. Background technique [0004] Peripheral blood stem cell transplantation (PBSCT) is a new technique to obtain progenitor and / or stem cells from a patient's blood and use them to restore the immune system of patients undergoing chemotherapy and / or radiation therapy (including, in some cases, blood donors). To obtain stem cells, these cells must be transferred or engrafted from the bone marrow into the peripheral blood. The strongest marker of this transplant success (determin...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/40
CPCA61K45/06A61K31/401A61P35/00A61P35/02A61P43/00A61K2300/00
Inventor G·布里杰L·M·佩鲁斯
Owner GENZYME CORP
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