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Therapeutic recombinant antibody, its coding gene and application

A therapeutic antibody and recombinant antibody technology, applied in the direction of antibody, recombinant DNA technology, drug combination, etc., can solve the problems of obvious side effects, large molecular weight, small molecular weight, etc., to inhibit occurrence and growth, increase retention time, penetration speed fast effect

Active Publication Date: 2020-07-24
DUBU BIOSCIENCES
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  • Abstract
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  • Claims
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Problems solved by technology

[0004] Full-length antibodies have been widely used in tumor treatment and have achieved good therapeutic effects. However, due to their large molecular weight, it is difficult to overcome the internal pressure of the tumor, and the speed of penetrating blood vessels to reach the tumor site is slow. Long antibodies circulate in the body for a long period, which is likely to cause a large immune response and obvious side effects; these factors greatly reduce the therapeutic effect of full-length antibodies
[0005] Fab (Fragment antigen binding) antibody has a molecular weight of about 50kDa and is the functional region of a full-length antibody molecule. It is composed of two chains vL-cL and vH-cH1. Due to its small molecular weight and strong penetrating power, it does not contain Fc Section, low immunogenicity, Fab antibody has been widely used in tumor therapy and targeted drug delivery, but the inhibitory effect of Fab antibody on tumor cells is still far behind that of the full-length antibody cetuximab

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  • Therapeutic recombinant antibody, its coding gene and application
  • Therapeutic recombinant antibody, its coding gene and application
  • Therapeutic recombinant antibody, its coding gene and application

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Embodiment Construction

[0037] As an aspect of the present invention, as mentioned above, in view of the many defects in the prior art, the inventors of the present case have produced a CBD-Fab fusion antibody with collagen-specific binding ability after long-term research and extensive practice. The fusion expression of the collagen-specific binding polypeptide and the functional region of the therapeutic antibody not only increases the targeting of the antibody, but also improves the penetration speed of the antibody, and it has been proved by in vitro and in vivo experiments that the CBD-Fab antibody can efficiently bind to collagen In combination, the abundant collagen in the tumor site can be used to increase the targeting of the fusion protein, that is, the CBD-Fab antibody can be enriched in the collagen-rich tumor site to form a higher local antibody concentration to kill the tumor and play a role in tumor cells. Similar to the effect of the full-length antibody cetuximab, the CBD-Fab antibody...

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Abstract

The invention discloses a therapeutic recombinant antibody, and an encoding gene and application thereof. In an excellent embodiment, the therapeutic recombinant antibody is mainly formed by fusion of CBD collagen specific-binding polypeptide and an Fab segment of cetuximab, and contains a light-chain variable region formed by a genetic code with a sequence shown by SEQ ID NO:1 and a heavy-chain variable region which is formed by a genetic code with a sequence shown by SEQ ID NO:2. The therapeutic recombinant antibody disclosed by the invention not only has the specific-binding capacity of collagen but also reserves the EGFR binding capacity of the cetuximab, and besides, the functions of killing tumor cells and suppressing tumor growth of the cetuximab are also maintained; and in addition, the recombinant antibody has high targeting ability and good tumor tissue infiltration capacity in bodies and can realize slow release in tumor tissues, the anti-tumor effects of the therapeutic recombinant antibody are far better than those of a total-length antibody namely the cetuximab, and the therapeutic recombinant antibody has wide application prospects in tumor detection preparations, antitumor medicines and the like.

Description

technical field [0001] The invention relates to a therapeutic antibody, in particular to a CBD-Fab fusion antibody with collagen-specific binding ability, its preparation method and its application in tumor treatment. Background technique [0002] The tumor microenvironment is composed of tumor cells, normal cells and extracellular matrix, and plays an important role in the occurrence and migration of tumors. Studies have shown that the occurrence of tumors is not only the canceration of cells, but also the microenvironment of cells and cells. Caused by dissonance between environments. Therefore, the tumor microenvironment plays an important role in the process of tumor migration. Collagen is the main component of the extracellular matrix and the main component of the tumor microenvironment. In the process of tumorigenesis, the extracellular matrix in the tumor microenvironment and the Compared with collagen, the expression of extracellular matrix in normal tissues is signi...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K19/00C12N15/62G01N33/574A61K39/395A61K47/64A61P35/00
Inventor 戴建武梁辉陈冰
Owner DUBU BIOSCIENCES
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