Chimeric antigen receptor based on human mesothelin antibody, lentiviral expression vector and applications of chimeric antigen receptor

A technology of chimeric antigen receptor and lentivirus, which is applied in the direction of anti-receptor/cell surface antigen/cell surface determinant immunoglobulin, virus/bacteriophage, receptor/cell surface antigen/cell surface determinant, etc. Solve the problems of unsatisfactory effect, exhaustion, T cell incompetence, etc., and achieve the effect of improving the therapeutic effect, improving the therapeutic effect, and increasing the killing activity

Active Publication Date: 2019-04-12
THE FIRST AFFILIATED HOSPITAL OF ZHENGZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

CAR-T cell therapy shows good results in hematological tumors, but unsatisfactory results in solid tumors
The shortcomings of CAR-T cells in the treatment of solid tumors are related to the following three issues: 1. Whether the source of the recognition region

Method used

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  • Chimeric antigen receptor based on human mesothelin antibody, lentiviral expression vector and applications of chimeric antigen receptor
  • Chimeric antigen receptor based on human mesothelin antibody, lentiviral expression vector and applications of chimeric antigen receptor
  • Chimeric antigen receptor based on human mesothelin antibody, lentiviral expression vector and applications of chimeric antigen receptor

Examples

Experimental program
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Effect test

Embodiment Construction

[0019] The experimental methods in the following examples are conventional methods unless otherwise specified, and the involved experimental reagents and materials are conventional biochemical reagents and materials unless otherwise specified.

[0020] 1. CAR Structure

[0021] The basic structure of meso-CAR consists of human CD8a molecule signal peptide (Leading signal), human mesothelin single-chain antibody (scFv), human CD8a molecule flexible fragment (CD8Hinge), human CD28 molecule transmembrane region and intracellular region (CD28) , human 41BB molecular intracellular region (41BB) and human CD3z molecular intracellular region (CD3z) are sequentially connected in series, and the structure formed in series is as follows figure 1 shown. The amino acid sequence of the meso-CAR structure is shown in SEQ ID NO.7.

[0022] Wherein, the amino acid sequence of human CD8a molecular signal peptide (Leading signal) is:

[0023] MALPVTALLLPLALLLLHAARP (SEQ ID NO.1)

[0024] Th...

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Abstract

The invention belongs to the field of biotechnology, and particularly relates to a chimeric antigen receptor based on a human mesothelin antibody, a lentiviral expression vector and applications of the chimeric antigen receptor. The chimeric antigen receptor is composed of a human CD8a molecular signal peptide, a humanized mesothelin single-chain antibody, a human CD8a molecular flexible fragment,a human CD28 molecular transmembrane region and intracellular region, a human 41BB intracellular region, and a human CD3z intracellular region which are sequentially connected in series. The chimericantigen receptor prepared by the invention can target mesothelin and improve the therapeutic effect of CAR-T cells.

Description

technical field [0001] The invention belongs to the field of biotechnology, and in particular relates to a chimeric antigen receptor based on human mesothelin antibody, a lentivirus expression vector and applications thereof. Background technique [0002] Mesothelin is highly expressed in a variety of tumors and is a good target for tumor therapy. Using transgenic technology, the chimeric antigen receptor (CAR) sequence that recognizes mesothelin is transfected into T cells, and CAR-T cells that specifically recognize mesothelin and kill tumor cells can be generated. CAR-T cell therapy has shown good results in hematological tumors, but the effect in solid tumors is unsatisfactory. The shortcomings of CAR-T cells in the treatment of solid tumors are related to the following three issues: 1. Whether the source of the recognition region of CAR-T cells is human or other species; Signals from the external recognition region are transmitted to the intracellular activation regio...

Claims

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Application Information

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IPC IPC(8): C07K19/00C12N15/62C12N15/867C12N7/01C12N5/10
CPCC12N7/00C12N15/86C07K14/7051C07K16/30C07K2319/33C07K2319/02C07K2317/622C12N2740/15043C12N2740/15021
Inventor 张毅李峰张震
Owner THE FIRST AFFILIATED HOSPITAL OF ZHENGZHOU UNIV
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