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Antibodies binding to an intracellular prl-1 or prl-3 polypeptide

A PRL-1 and antibody technology, applied in the medical field, can solve the problems that antibodies cannot pass through the cell membrane and cannot access antigens

Active Publication Date: 2010-09-01
AGENCY FOR SCI TECH & RES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Antibodies have not so far been used to target intracellular antigens or cancer markers because antibodies cannot pass through cell membranes and thus cannot access antigens

Method used

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  • Antibodies binding to an intracellular prl-1 or prl-3 polypeptide
  • Antibodies binding to an intracellular prl-1 or prl-3 polypeptide
  • Antibodies binding to an intracellular prl-1 or prl-3 polypeptide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 27

[0078] Example 27 shows that anti-PRL1 antibody 269 can bind to epitopes TYKNMR and TLNKFI. Therefore, the present inventors provide an anti-PRL antibody such as an anti-PRL1 antibody capable of binding to the sequence TYKNMR. The present inventors also provide anti-PRL antibodies such as anti-PRL1 antibodies capable of binding to TLNKFI. The anti-PRL antibody may have the ability to simultaneously bind to these two sequences.

[0079] Furthermore, Example 27 shows that the anti-PRL3 antibody can bind to the epitopes KAKFYN and HTHKTR. Therefore, the present inventors provide an anti-PRL antibody such as an anti-PRL3 antibody capable of binding to the sequence KAKFYN. The present inventors also provide anti-PRL antibodies such as anti-PRL3 antibodies capable of binding to HTHKTR. The anti-PRL antibody may have the ability to simultaneously bind to these two sequences.

[0080] The anti-PRL antibody may comprise the variable region of antibody 269, the variable region of antibod...

Embodiment 9

[0096] Example 9 records the generation of PRL overexpressing tumors in mice, and provides an animal model for metastasis and cancer treatment. Examples 10-12 show that animals treated with anti-PRL antibodies show significantly lower metastatic lung tumors compared to animals not treated with anti-PRL antibodies. Specifically, the treated animals showed about 90% fewer tumors than untreated animals. The anti-PRL antibody can bind to the PRL polypeptide and block its activity, even though the PRL polypeptide is localized in the cell. The inventor's research represents the first examples of how effective (about 90%) of metastasis can be blocked by using monoclonal antibodies against the respective phosphatases (although they are localized in the cell).

[0097] The inventors also showed that the anti-PRL-3 monoclonal antibody can effectively block the formation of metastases in the human ovarian cancer cell line A2780 expressing endogenous PRL-3 protein.

[0098] Therefore, the pr...

Embodiment 1

[0497] Example 1. Cell lines: CHO-K1, A2780 and CT26

[0498] CHO-K1 cells, A2780 human ovarian cancer cells and CT26 mouse colon cancer cells were purchased from ATCC (Manassas, VA).

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PUM

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Abstract

We provide an antibody capable of binding to an intracellular PRL-I or PRL-3 polypeptide, in which the antibody is capable of binding to an epitope bound by antibody 269, antibody 223 or antibody 318. Such anti-PRL antibodies may be capable of binding to intracellular PRL-I or PRL-3. They may be suitable for use as therapies against cancer or metastasis thereof, or in clinical diagnosis to identify PRL-3 or PRL-I positive patients.

Description

Technical field [0001] The invention relates to the medical field, cell biology field, molecular biology field and biochemistry field. The invention also relates to the medical field. [0002] In particular, the present invention relates to the treatment and diagnosis of diseases, especially cancer, and compositions for such uses. Background technique [0003] Cancer is a serious health problem all over the world. In 2007, it is estimated that 7.6 million people worldwide died of cancer. For example, in the UK, cancer causes 126,000 deaths every year. One in four people die from cancer. [0004] Known treatments for cancer include surgery, chemotherapy, and radiation therapy. If detected early enough, many cancers can be cured. [0005] 100 years ago, the German chemist Paul Ehrlich proposed the concept of antibodies as a "rubic cube". Antibodies can recognize and bind their antigens in a special way, so they are ideal agents for the immune system to recognize and destroy malign...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61P35/00C07K16/18
CPCC07K2317/24A61K39/39558C07K2317/76C07K2317/77C07K16/40C07K2316/96A61K2039/505C07K16/18G01N33/57496C07K2317/34C07K2317/56C07K2317/73C07K16/30G01N2333/916A61P35/00A61P35/04A61K39/395A61K39/3955C12N5/0693C12N15/52G01N33/5005G01N33/53
Inventor 曾琦
Owner AGENCY FOR SCI TECH & RES
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