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Hematopoietic stem cell proliferation promoter

A technology of hematopoietic stem cells and accelerators, which is applied in the field of hematopoietic function recovery accelerators, and can solve the problem of no hematopoietic stem cells yet.

Inactive Publication Date: 2009-08-05
CHUGAI PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] As described above, there has been no report so far of actually successfully activating the proliferation of hematopoietic stem cells by administering an antibody having TPO receptor agonistic activity

Method used

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  • Hematopoietic stem cell proliferation promoter
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  • Hematopoietic stem cell proliferation promoter

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0387] [Example 1] TPO receptor agonist affects human blood cells in bone marrow of artificial hematopoiesis reconstituted mice The effect of birth number

[0388] In order to study the effect of sc(Fv)2 antibody (hVB22 u2-wz4: sc(Fv)2) comprising the amino acid sequence described in SEQ ID NO: 73 on human hematopoietic system regeneration at the initial stage after transplantation of hematopoietic stem cells derived from human umbilical cord blood To determine the influence of the number of human blood cells in the bone marrow of mice, the experiment was carried out in the following way. It should be noted that the sc(Fv)2 antibody comprising the amino acid sequence described in SEQ ID NO: 73 can be prepared according to the method described in WO2005 / 056604.

[0389] method

[0390] Mice used domesticated 6-week-old male NOD.CB17-Prkdc / J. After the whole body of the mouse was irradiated with 3.0 Gy of X-rays, the anti-asialo-GM1 antibody was administered...

Embodiment 2

[0393] [Example 2] TPO receptor agonists have an effect on human CFU-Meg in the bone marrow of artificial hematopoiesis remodeled mice Effect of colony number

[0394] In order to investigate the effect of the sc(Fv)2 antibody described in SEQ ID NO: 73 on the number of human CFU-Meg colonies after transplantation of hematopoietic stem cells derived from human umbilical cord blood, the following experiments were performed.

[0395] method

[0396] Mice used domesticated 6-week-old male NOD.CB17-Prkdc / J. After the whole body of the mouse was irradiated with 3.0 Gy of X-rays, the anti-asialo-GM1 antibody was administered intraperitoneally once every 10 days from the day of irradiation. On the second day after irradiation, 5×10 mice were transplanted via the tail vein. 4 CD34-positive cells from human umbilical cord blood. The sc(Fv)2 antibody described in SEQ ID NO: 73 was administered for 10 consecutive days from the second day after the transplantation, ...

Embodiment 3

[0399] [Example 3] TPO receptor agonist affects human blood cells in bone marrow of artificial hematopoiesis reconstituted mice Dose-dependent effect of raw numbers

[0400] In order to study the dose-dependent effect of the sc(Fv)2 antibody described in SEQ ID NO: 73 on the number of human blood cells in the bone marrow of reconstituted mice after transplantation of hematopoietic stem cells from human umbilical cord blood, the following experiments were carried out .

[0401] method

[0402] Mice used domesticated 6-week-old male NOD.CB17-Prkdc / J. After the whole body of the mice was irradiated with 3.0 Gy of X-rays, an anti-asialo-GM1 antibody was administered intraperitoneally on the day of irradiation and 8 days after the irradiation. On the second day after irradiation, 5×10 mice were transplanted via the tail vein. 4 CD34-positive cells from human umbilical cord blood. The sc(Fv)2 antibody described in SEQ ID NO: 73 was administered for 10 consecu...

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Abstract

The present inventors discovered that the administration of an agonistic minibody (VB22B sc(Fv)2) against the TPO receptor resulted in not only the induction of human megakaryocyte-specific differentiation (increase in platelet precursor cells), but also the engraftment of transplanted hematopoietic stem cells derived from human cord blood (CD34-positive cells) and significant increase in multi-lineage hematopoietic precursor cells. TPO and TPO receptor agonists can be used as agents for promoting the growth of CD34-positive hematopoietic cells or agents for promoting the engraftment of transplanted cells in the bone marrow, which can be effective when administered alone (without using G-CSF and erythropoietin in combination) after hematopoietic stem cell transplantation (in particular, cord blood transplantation). Furthermore, TPO and TPO receptor agonists can be used as agents for promoting the growth and / or differentiation of multilineage hematopoietic precursor cells and agents for promoting the recovery of multilineage hematopoiesis.

Description

technical field [0001] The present invention relates to a hematopoietic stem cell proliferation promoter containing a TPO receptor (c-mpl) agonist as an active ingredient. The present invention also relates to an agent for promoting the proliferation and / or differentiation of hematopoietic CD34 positive cells containing a TPO receptor (c-mpl) agonist as an active ingredient, and promoting the engraftment of hematopoietic CD34 positive cells in bone marrow agent, and hematopoietic recovery promoter in hematopoietic stem cell transplantation. Background technique [0002] Thrombopoietin (TPO) is a cytokine that promotes the proliferation and differentiation of hematopoietic cells in the megakaryocyte system, and is known as a ligand for megakaryocyte colony-stimulating factor (Megakaryocyte colony-stimulating factor) or c-mpl. Most cytokine receptors combine with ligands to form dimers between receptors and transmit signals to cells. It has been reported that TPO binds to it...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K39/395A61P35/02A61P43/00A61P7/06
Inventor 吉久保尚司椎名雅史稻垣友纪子
Owner CHUGAI PHARMA CO LTD
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