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Monoclonal antibody targeting human claudin18.2 protein and its application

A monoclonal antibody, protein technology, applied in the field of biological cells, can solve problems such as frequent ectopic activation

Active Publication Date: 2022-08-05
SHENZHEN FIRST CONDOR BIOSCIENCE CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The expression distributions of Claudin 18.1 and Claudin 18.2 are different, Claudin18.1 is selectively expressed in normal lung cells, and Claudin 18.2 is highly restricted in normal cells, but in a variety of tumors (such as gastric cancer, lung cancer and pancreatic cancer frequent ectopic activation and overexpression in

Method used

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  • Monoclonal antibody targeting human claudin18.2 protein and its application
  • Monoclonal antibody targeting human claudin18.2 protein and its application
  • Monoclonal antibody targeting human claudin18.2 protein and its application

Examples

Experimental program
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Effect test

Embodiment 1

[0118] The preparation method and functional verification of the antibody of the present embodiment include the following steps:

[0119] S100: Mouse immunization and sequence acquisition of mouse monoclonal antibody

[0120] Balbc mice were immunized with self-produced human Claudin18.2 protein, and the mice were immunized by subcutaneous multi-point injection at 20ug / mice / time, once a week. After 4 weeks of immunization, mice whose blood antibody titers reached more than 1k were sacrificed, and the spleen cells were fused with SP2.0 cells. The titer of the fusion cells was tested, and the positive fusion cells were screened to pick monoclonal cells by limiting dilution method, and then carry out antibody fermentation and functional evaluation. The final screened mouse monoclonal antibody was extracted, and the antibody light and heavy chain expression plasmid was constructed to ferment and purify the antibody and Construction of CAR plasmids.

[0121] S200: Fermentation an...

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PUM

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Abstract

The invention relates to the technical field of biological antibodies, in particular to a monoclonal antibody targeting human Claudin18.2 protein and its application. The monoclonal antibody includes a heavy chain variable region HV and a light chain variable region LV, and the amino acid sequence and nucleic acid sequence of the monoclonal antibody can be used in a single chain or a combination of double chains. The monoclonal antibody can specifically recognize human Claudin18.2 antigen, but not human Claudin18.1 antigen, and has good specificity in human normal tissues, only binds to Claudin18.2 positive tissues, and does not recognize other tissues and organs, and has no off-target risk. The monoclonal antibody has a specific antibody-mediated complement-dependent (CDC) killing effect on Claudin18.2 positive target cells, and the CAR-T prepared by the monoclonal antibody has a specific killing function on Claudin18.2 positive target cells.

Description

technical field [0001] The invention relates to the technical field of biological cells, in particular to a monoclonal antibody targeting human Claudin18.2 protein, which can be used as a biological material for the construction of other DNA vectors, recombinant protein expression, cell line construction and chimeric antigen receptors In immune cells; or after coupling with other substances, it can be used as a biological agent, or it can be used directly as a biological agent. Background technique [0002] Claudins, a family of proteins that maintain tight junctions that control molecular exchange between cells, are widely distributed in stomach, pancreas, and lung tissues and can be used for disease diagnosis and treatment. The CLDN18.2 (i.e., Claudin18.2) isoform, as a gastric-specific isoform, has become a ideal target. CLDN18.2 is usually buried in the gastric mucosa, and the monoclonal antibodies in normal tissues are basically inaccessible. The occurrence of maligna...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K16/28C07K16/30C12N15/13G01N33/577G01N33/574G01N33/68C07K19/00C12N15/867C12N5/10
CPCC07K16/28C07K16/3046C07K16/3023C07K16/303C07K16/30G01N33/577G01N33/57446G01N33/57438G01N33/57423G01N33/57407G01N33/57492G01N33/68C07K14/7051C12N15/86C12N5/0636C07K2317/56C07K2317/565C07K2317/734C07K2317/92C07K2317/33C07K2317/622G01N2333/705C07K2319/02C07K2319/03C07K2319/33C12N2740/15043C12N2800/107C12N2510/00Y02A50/30
Inventor 谢海涛都晓龙马丽雅
Owner SHENZHEN FIRST CONDOR BIOSCIENCE CO LTD
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