Chimeric antigen receptor (CAR) and application thereof

A technology of chimeric antigen receptors and antigens, applied in the field of cell therapy, can solve the problems of high toxicity and side effects, poor curative effect, etc., achieve the effects of reducing production costs, preventing lentiviral DNA recombination, and increasing feasibility

Active Publication Date: 2020-04-10
GUANGZHOU YIYANG BIO TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Scientists have made many attempts in this regard, but the curative effect is often poor and the side effects are too large to continue.

Method used

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  • Chimeric antigen receptor (CAR) and application thereof
  • Chimeric antigen receptor (CAR) and application thereof
  • Chimeric antigen receptor (CAR) and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] 1. Preparation of PD-L1 single chain antibody

[0042] PD-L1-specific single-chain antibody derived from atezolizumab antibody, which has: heavy chain variable region (PD-L1V H ) and light chain variable region (PD-L1 V L ). The heavy chain variable region and the light chain variable region are linked by a linker chain (PD-L1-Linker). Among them: Atezolizumab is a humanized PD-L1 monoclonal antibody approved by the US FDA for the treatment of lung cancer. It is highly specific for human PD-L1. The PD-L1 single-chain antibody / receptor can be expressed in human T cells by using the gene fragments of its heavy chain (H) and light chain (L) variable regions after certain modifications.

[0043] PD-L1 V H The amino acid sequence is shown in SEQ ID NO.1, and the nucleotide sequence is shown in SEQ ID NO.2;

[0044] PD-L1 V L The amino acid sequence is shown in SEQ ID NO.3, and the nucleotide sequence is shown in SEQ ID NO.4;

[0045] The amino acid sequence of PD-L1-...

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Abstract

The invention discloses a PD-L1 CAR structure, a specific structure of a CAR sequence of the PD-L1 CAR structure is as follows: a CD8 alpha leading peptide-PD-L1 scFv-CD8 alpha transmembrane region, aCD137 intracellular costimulatory domain, a CD247 intracellular activation domain. Tumor targeting and T cell double-activation pathway molecules are integrated into a single PD-L1 chimeric receptorgene, so that the feasibility of treating solid tumors by genetically modified T cells is greatly improved, the preparation cost is reduced, and the product can be applied to treatment of PD-L1 high-expression solid tumors, such as lung cancer, liver cancer, colon cancer and the like.

Description

technical field [0001] The invention relates to the technical field of cell therapy, in particular to a chimeric antigen receptor (CAR) and its application. Background technique [0002] When T lymphocytes play an anti-tumor role, they recognize and kill tumor cells through the TCR (T cell receptor, T cell receptor) on their surface. However, studies have found that the expression of PD-L1 (Programmed death ligand 1, programmed cell death receptor ligand 1) in a variety of tumor cells is up-regulated, and PD-L1 binds to the receptor PD-1 of T cells, thereby inhibiting T cells. Cell proliferation and activation make T cells inactive, resulting in immune escape of tumor cells. [0003] Genetic modification of immune cells in vitro can enable T cells to recognize new targets and be activated to kill tumor cells. Among them, chimeric antigen receptor (Chimeric Antigen Receptor, CAR) is a single-chain antibody (scFv) against a certain antigen and T cell activation signal (CD28 / ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/28C12N15/13C07K19/00C12N15/62C12N15/867C12N5/10A61K39/00A61P35/00
CPCA61K39/001111A61K2039/5156A61K2039/804A61K2039/82A61K2039/844A61K2039/86A61P35/00C07K14/7051C07K16/2827C07K2317/56C07K2317/622C07K2319/02C07K2319/03C07K2319/33C07K2319/74C12N5/0636C12N15/86C12N2510/00C12N2740/15043C12N2800/107
Inventor 刘和平夏商周姜结根何玉凯万阳夏黎明
Owner GUANGZHOU YIYANG BIO TECH CO LTD
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