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Anti-tspan8 monoclonal antibody and use thereof

An antibody and carrier technology, applied in the direction of antibodies, applications, anti-tumor drugs, etc., can solve the problem of lack of fully human antibodies, and achieve the effect of strong specificity, inhibition of tumor growth, and high affinity

Active Publication Date: 2021-04-30
SHANGHAI FIRST PEOPLES HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] At present, there is still a lack of fully human antibodies against TSPAN8 with high affinity anti-tumor effects in China

Method used

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  • Anti-tspan8 monoclonal antibody and use thereof
  • Anti-tspan8 monoclonal antibody and use thereof
  • Anti-tspan8 monoclonal antibody and use thereof

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Experimental program
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Effect test

Embodiment

[0052] A method for obtaining a monoclonal antibody against TSPAN8. In this embodiment, the constant region of the heavy chain of the IgG1 subtype and the constant region of the light chain comprising kappa are selected. The brief description includes the following steps:

[0053] S1: The gene sequence encoding the extracellular segment of TSPAN8 (TSPAN8-LEL) and the C-terminal FC-tag were cloned into the pFUSE expression vector by gene recombination technology, and the human TSPAN8-LEL-FC fragment was constructed and expressed in HEK293F cells Obtain TSPAN8-LEL-FC fusion protein;

[0054] S2: Using the TSPAN8-LEL-FC fusion protein as the antigen, through three rounds of antibody library enrichment screening, eight high-affinity ScFv sequences were obtained from the fully human ScFv phage library, which were named TsC01-TsC08.

[0055] S3: The above eight positive ScFv sequences, namely TsC01-TsC08, were cloned into eukaryotic expression vectors, expressed and purified after t...

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Abstract

The present invention discloses an anti-TSPAN8 monoclonal antibody and its use. The antibody can specifically bind to TSPAN8 protein; the heavy chain variable region of the antibody consists of the nucleic acid sequence shown in SEQ ID NO: 1 or its homologous The light chain variable region of the antibody is encoded by the nucleic acid sequence shown in SEQ ID NO: 2 or its homologous sequence, which can be used for the preparation of treatment and / or prevention of TSPAN8-mediated promotion of tumor cell epithelial interepithelial The molecular regulatory mechanism of qualitative transformation and stemness enhancement and the pharmaceutical composition of key molecular targets for diseases. The anti-TSPAN8 monoclonal antibody provided by the invention has high affinity, strong specificity and good stability, and has the ability to inhibit the proliferation and migration of breast cancer cell lines, and can inhibit the growth of tumors.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to a fully human anti-TSPAN8 monoclonal antibody and its application. Background technique [0002] Tetraspanins, also known as the tetraspanins superfamily (TM4SF), consist of 33 family members, including TSPAN8, CD63, CD37, CD53, CD81 and CD9 related to differentiation (CD). The common feature of the Tetraspanins family is that they have four highly conserved membrane spanning domains, which play important biological regulation in various cellular functions. [0003] Tumor invasion, metastasis and drug resistance are the main causes of clinical treatment failure and patient death. In the tumor microenvironment (Tumor Microenvironment, TME), the tetraspanning protein TSPAN8 promotes the molecular regulation mechanism and key molecular targets of tumor cell epithelial-mesenchymal transition (Epithelial Mesenchymal Transition, EMT) and stemness (Stemness). Accumulating evidence shows tha...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K16/28C12N15/13A61K39/395A61P35/00A61P35/04
CPCA61K2039/505A61P35/00A61P35/04C07K16/28C07K2317/73C07K2317/92
Inventor 王红霞葛伟玉杨光朱容萱马培祥周天浩李军建许静轩
Owner SHANGHAI FIRST PEOPLES HOSPITAL