Single-chain antibody targeting OX40, chimeric antigen receptor T-lymphocyte and preparation method and application thereof

A chimeric antigen receptor and single-chain antibody technology, applied in the field of medical biology, can solve the problems of failing to kill tumor cells, achieve high infection efficiency and transcription efficiency, avoid immune response, and good targeting effects

Inactive Publication Date: 2019-07-02
SHENZHEN BINDEBIOTECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there is no preparation and research of chimeric antigen receptor T cells targeting OX40
In addition, the in vivo maintenance ability (persistence) of CAR-T cells is the guarantee of the long-term efficacy of CAR-T, but in fact, CAR-T completely disappears after a few days to a few weeks after reinfusion, and fails to exert a long-lasting and lasting effect. ability to kill tumor cells

Method used

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  • Single-chain antibody targeting OX40, chimeric antigen receptor T-lymphocyte and preparation method and application thereof
  • Single-chain antibody targeting OX40, chimeric antigen receptor T-lymphocyte and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0071] A method for preparing chimeric antigen receptor T cells targeting OX40, comprising the following steps:

[0072](1) Prepare the gene sequence of chimeric antigen receptor CAR-OX40 targeting OX40

[0073] The coding genes of the signal peptide, the single-chain antibody targeting OX40, the CD8α hinge region, the CD8 transmembrane region, the CD27 signal region and the CD3ζ signal region were respectively prepared. The coding gene sequence of the signal peptide is shown in SEQ ID NO: 15, The coding gene sequence of the single-chain antibody targeting OX40 is shown in SEQ ID NO: 2, the coding gene sequence of the CD8α hinge region is shown in SEQ ID NO: 7, and the coding gene sequence of the CD8 transmembrane region is shown in As shown in SEQ ID NO: 9, the coding gene of the CD27 signal region is shown in SEQ ID NO: 11, and the coding gene of the CD3ζ signal region is shown in SEQ ID NO: 13.

[0074] The genes encoding the signal peptide, the single-chain antibody targe...

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PUM

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Abstract

The invention provides a single-chain antibody targeting OX40. The single-chain antibody targeting OX40 includes an amino acid sequence as shown in SEQ-ID-NO:1. The single-chain antibody targeting OX40 is a humanized single-chain antibody. The invention also provides a chimeric antigen receptor T-lymphocyte including the single-chain antibody targeting OX40, and the chimeric antigen receptor targeting OX40 can specifically target the tumor cells expressing OX40 and promote the proliferation of T-lymphocyte in vivo in patients, thereby killing and wounding the tumor cells efficiently and specifically. In addition, the chimeric antigen receptor T-lymphocyte targeting OX40 prepared by the humanized single-chain antibody can better maintain cell viability and lethality. The invention also provides a preparation method and an application of the chimeric antigen receptor T-lymphocyte targeting OX40.

Description

technical field [0001] The invention relates to the field of medical biology, in particular to a single-chain antibody targeting OX40, a chimeric antigen receptor T cell, and a preparation method and application thereof. Background technique [0002] Malignant tumor (cancer) has become the culprit threatening human life, and the incidence rate is on the rise. OX40 (also known as CD134), as a member of the tumor necrosis factor receptor (TNFR) superfamily, has been found to be highly expressed in specific types of lymphomas, and can be used as a target for CAR-T therapy of lymphomas. CAR-T (Chimeric Antigen Receptor T Cell) technology is a new type of cell therapy, which is to reinfuse CAR-modified T cells into the human body, activate the autoimmune system, and kill tumor cells. One of the effective ways to treat malignant tumors. At present, there is no preparation and research of chimeric antigen receptor T cells targeting OX40. In addition, the in vivo maintenance abil...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/28C07K5/10C12N15/867A61P35/00
CPCA61K35/17C07K14/7051C07K16/2875C07K2317/622C07K2319/02C07K2319/33C12N5/0636C12N15/86C12N2510/00C12N2740/15043
Inventor 张宏玲龙丽梅钟春颖
Owner SHENZHEN BINDEBIOTECH CO LTD
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