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Monoclonal antibody targeted to human tumor stem cells and application thereof

A monoclonal antibody and tumor stem cell technology, applied in the field of biomedicine, can solve the problems that cancer patients cannot obtain

Active Publication Date: 2017-09-15
SUZHOU BOJUHUA BIOMEDICAL TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The emerging tumor immunotherapy methods in the past two years, such as PD-1 monoclonal antibody drugs targeting immune checkpoints and CAR-T cell therapy, have shown some encouraging signs of long-term efficacy, but the overall The effective rate of cancer patients can only reach about 20-30%, and there are still a large number of cancer patients who cannot be treated with truly effective drugs

Method used

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  • Monoclonal antibody targeted to human tumor stem cells and application thereof
  • Monoclonal antibody targeted to human tumor stem cells and application thereof
  • Monoclonal antibody targeted to human tumor stem cells and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0114] The present inventors found that the target antigen of the monoclonal antibody Hetumomab of the present invention is expressed on the surface of living cells of various human tumor cells, and is highly specifically expressed in various tumor tissues (positive rate 79%-94%). The Hetumomab monoclonal antibody of the present invention can be enriched in the sphere cultured cells of various tumor cells and can recognize tumor cells of tumor stem cell markers such as ESA and CD90, suggesting that Hetumomab monoclonal antibody is a monoclonal antibody specifically directed at tumor stem cells (implementation Example 2).

[0115] Further studies based on Hetumomab target antigen-positive tumor cells showed that, compared with parental tumor cells and Hetumomab target antigen-negative tumor cells, Hetumomab target antigen-positive tumor cells had stronger self-renewal, invasion, drug resistance and tumorigenic abilities in vivo. It was proved that Hetumomab monoclonal antibody ...

Embodiment

[0214] A further understanding of the invention may be obtained by reference to certain specific examples which are given herein for illustration only and are not intended to limit the scope of the invention in any way. Apparently, various modifications and changes can be made to the present invention without departing from the essence of the present invention. Therefore, these modifications and changes are also within the protection scope of the present application.

[0215] Example 1 Preparation of Mouse Monoclonal Antibody Hetumomab

[0216] 1. Preparation of mouse monoclonal antibody library against human tumor pluripotent stem cells

[0217] In this example, a human tumor pluripotent stem cell line T3A-A3 was used as the immunogen (Liu H, et al. Cell Death and Disease. 2013, 4: e857). The human tumor stem cell line is obtained from the liver cancer tissue resected by primary liver cancer patients, and can be cultured in vitro for a long time. . The cell line has been p...

Embodiment 2

[0226] Example 2 Hetumomab target antigens are specifically expressed in various tumor cells and tissues

[0227] 1. The target antigen of Hetumomab is expressed in various human liver cancer, lung cancer and gastric cancer cell lines and can be expressed on the surface of living cells.

[0228] The expression of the target antigen of monoclonal antibody Hetumomab in various human tumor cell lines such as liver cancer, lung cancer, and gastric cancer cell lines on the surface of living cells was detected by conventional living cell immunofluorescence staining technology. The specific technical methods are roughly as follows: cell climbing or inoculation into 96-well culture plates (4×10 3 cells / well), and when the cells grew to 60%-70% full, they were washed twice with serum-free medium and once with PBS. Add primary antibody (hybridoma supernatant or purified antibody), mouse anti-α-tublin antibody (dilution 1:1000) as the control of cell permeability, normal mouse IgG, SP2 / ...

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Abstract

The invention relates to the field of biomedicines, and particularly relates to a separated monoclonal antibody, or an antigen-binding fragment thereof, targeted to human tumor stem cells, and applications of the antibody or the fragment in tumor therapy and diagnosis.

Description

technical field [0001] The invention relates to the field of biomedicine. Specifically, the present invention relates to an isolated monoclonal antibody or an antigen-binding fragment thereof against human tumor stem cells, and the use of the antibody or fragment in tumor treatment and diagnosis. Background technique [0002] Malignant tumor (cancer) has become the "number one killer" that threatens the life and health of people all over the world. The number of cancer patients in the world exceeds 14 million every year, and the number of new cancer patients in my country alone exceeds 3 million every year. [0003] The root cause of the high mortality rate of cancer is the proliferation and metastasis of cancer cells and the relapse and drug resistance of most patients after treatment. The existing clinical treatment methods, such as surgery, radiotherapy, and chemotherapy, have little effect on cancer cell metastasis, recurrence, and drug resistance, or only have a short...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/30C12N15/13C12N5/095A61K39/395A61P35/00A61P35/04G01N33/574
CPCA61K2039/505C07K16/30C07K2317/33C07K2317/56C07K2317/565C07K2317/73C07K2317/76C07K2317/92C12N5/0695G01N33/57415G01N33/57423G01N33/57434G01N33/57438G01N33/57446G01N33/57488G01N2800/50G01N2800/54
Inventor 沈敏
Owner SUZHOU BOJUHUA BIOMEDICAL TECH CO LTD