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Method for treating giant cell tumor of bone

A technology of giant cell tumor of bone, inhibitor, applied in the field of oncology and diagnosis, can solve the problem of patient recurrence and so on

Active Publication Date: 2021-09-17
SHANGHAI INST OF BIOLOGICAL SCI CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, both drugs have a range of side effects 11-13 , and patients are at risk of relapse after drug withdrawal

Method used

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  • Method for treating giant cell tumor of bone
  • Method for treating giant cell tumor of bone

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0207] Inhibition of CD44 reduces osteoclast formation in vitro

[0208] Firstly, the conditioned medium of SRGN-overexpressed hFOB1.19 cells and SRGN recombinant protein were used to induce the formation of osteoclasts in vitro.

[0209] The results showed that SRGN could significantly promote the formation of osteoclasts no matter using mouse primary bone marrow cells or RAW264.7 cell line. However, when a neutralizing antibody to CD44 was further added, the formation of osteoclasts was significantly inhibited ( figure 1 A-H).

[0210] In addition, the Cd44 gene was knocked out using CRISPR-Cas9 technology in RAW264.7 cells ( figure 1 I).

[0211] The results showed that after Cd44 was knocked out, neither the conditioned medium of SRGN overexpressed hFOB1.19 cells nor the SRGN recombinant protein could continue to promote the formation of osteoclasts ( figure 1 J-M).

[0212] These results demonstrate that inhibition of CD44 reduces osteoclast formation in vitro.

Embodiment 2

[0214] CD44 neutralizing antibody inhibits the formation of multinucleated giant cells and the growth of giant cell tumor of bone in mice

[0215]In this example, firstly, GCTB-19 giant cell tumor cells of bone were injected into immunodeficient NOD / SCID mice by way of tibial injection. One week after cell injection, mice were injected with CD44 neutralizing antibody or IgG control every two days. Since tumor cells are pre-labeled with luciferase, tumor cell growth can be tracked in vivo by injecting mice with a luciferase substrate for live imaging.

[0216] The results showed that in mice injected with CD44 neutralizing antibody, the growth of giant cell tumor of bone was significantly inhibited ( figure 2 A-C), and compared with the control group, the bone damage of these mice injected with CD44 neutralizing antibody was significantly alleviated, and the relative bone volume was also restored to a certain extent ( figure 2 A and D).

[0217] In addition, mouse leg bone...

Embodiment 3

[0219] Safety of CD44-targeted therapy

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Abstract

The invention relates to a method for treating giant cell tumor of bone. Specifically, the invention provides application of a CD44 inhibitor, and the CD44 inhibitor is used for preparing the medicine for treating the giant cell tumor of the bone. Experimental results of the invention show that, the SRGN can be used as a novel biological marker for predicting the giant cell tumor of the bone and is used for diagnosing, typing and / or treating the giant cell tumor of the bone. Besides, in the tissue of giant cell tumor of the bone, the fusiform stromal cells can secrete glycoprotein of SRGN and can interact with the CD44 receptor on the mononuclear cells, so that the mononuclear cells are promoted to be differentiated into multinuclear giant cells. Therefore, the CD44 can be used as a target for clinically treating the giant cell tumor of the bone.

Description

technical field [0001] The invention relates to the fields of oncology and diagnosis, and in particular, the invention relates to a method for treating giant cell tumor of bone. Background technique [0002] Giant cell tumor of bone is a common primary bone tumor 1 , usually occurs in the metaphysis of the long bones of the extremities, including the distal femur, proximal femur, and proximal tibia 2 . Although giant cell tumor of bone is generally considered a benign tumor and rarely metastasizes, it is locally aggressive and often results in severe bone destruction 3,4 . [0003] Currently, the diagnosis and treatment methods for giant cell tumor of bone are very limited. The diagnosis of giant cell tumor of bone is mainly through histopathological and radiological evaluation, as well as the detection of H3.3G34W mutation. [0004] Currently, treatment options for giant cell tumor of bone are limited. In terms of clinical treatment, surgery is the most commonly used ...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K31/7088A61K39/395A61K48/00A61K45/06A61P35/00C12Q1/6886G01N33/574G01N33/68
CPCA61K45/00A61K31/7088A61K39/39558A61K48/005A61K45/06A61P35/00C12Q1/6886G01N33/57484G01N33/57488G01N33/57407G01N33/6893C12Q2600/112C12Q2600/118C12Q2600/158A61K2300/00
Inventor 胡国宏贺云飞
Owner SHANGHAI INST OF BIOLOGICAL SCI CHINESE ACAD OF SCI
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