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Chimeric antigen receptor (CAR) targeting fibroblast activation protein (FAP), CAR-T cell targeting FAP, preparation method of CAR-T cell and application of CAR and CAR-T cell

A chimeric antigen receptor, targeting technology, applied in the field of medical biology, can solve problems such as side effects, poor treatment effect of ovarian cancer, and easy tumor recurrence.

Inactive Publication Date: 2019-12-03
SHENZHEN BINDEBIOTECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Traditional therapies such as radiotherapy and chemotherapy are not effective in the treatment of ovarian cancer, and there are problems such as easy tumor recurrence and serious side effects
However, there is no preparation and research of chimeric antigen receptor T cells targeting FAP

Method used

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  • Chimeric antigen receptor (CAR) targeting fibroblast activation protein (FAP), CAR-T cell targeting FAP, preparation method of CAR-T cell and application of CAR and CAR-T cell

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0073] A method for preparing chimeric antigen receptor T cells targeting FAP, comprising the following steps:

[0074] (1) Prepare the gene sequence of the chimeric antigen receptor CAR-FAP targeting FAP

[0075] The genes encoding the signal peptide, the single-chain antibody targeting FAP, the hinge region of CD8α, the transmembrane region of CD8, the signal region of CD27 and the signal region of CD3ζ were prepared respectively, and the genes encoding the signal peptide were shown in SEQ ID NO: 15. The coding gene of the single-chain antibody targeting FAP is shown in SEQ ID NO: 2, the coding gene of the CD8α hinge region is shown in SEQ ID NO: 7, and the coding gene of the CD8 transmembrane region is 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.

[0076] The genes encoding the above signal peptide, FAP-targeting single-chain antibody, CD8α hinge region, C...

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Abstract

The invention provides a chimeric antigen receptor (CAR) CAR-FAP targeting a fibroblast activation protein (FAP) and a CAR-T cell targeting the FAP. The CAR-FAP comprises a single-chain antibody targeting the FAP, an amino acid sequence of an extracellular hinge region, an amino acid sequence of a transmembrane region and an amino acid sequence of an intracellular signal region which are sequentially connected from an amino terminal to a carboxyl terminal, the CAR-FAP can specifically target tumor cells for expressing the FAP, a CD27 signal region serves as a co-stimulation signal region to activate the T cell to play the role of cell immunity, amplification of the T cell in a patient body is promoted, FAP positive tumor cells are killed efficiently and specifically, and the long-lasting cell vitality and lethality are achieved. The invention further provides a preparation method of the chimeric antigen receptor T cell targeting the FAP, a recombinant viral vector with CAR-FAP encodedgenes and the like.

Description

technical field [0001] The invention relates to the field of medical biology, in particular to a FAP-targeted chimeric antigen receptor, chimeric antigen receptor T cells, 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. For example, the mortality rate of malignant ovarian tumors ranks first among gynecological reproductive tract malignant tumors, and 60-70% of ovarian malignant tumor patients are already at an advanced stage when they are diagnosed. The abnormal expression of fibroblast activation protein (Fibroblast Activation Protein, FAP) may be related to the occurrence and development of ovarian cancer, which can promote the proliferation, invasion and migration of ovarian cancer cells. FAP is often expressed in ovarian cancer mesenchymal fibroblasts . Traditional therapies such as radiotherapy and chemotherapy have poor therap...

Claims

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Application Information

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IPC IPC(8): C07K19/00C12N5/10C12N15/62C12N15/867A61K35/17A61P35/00
CPCA61K35/17A61P35/00C07K14/7051C07K16/40C07K2317/622C07K2319/02C07K2319/03C07K2319/33C12N5/0636C12N15/86C12N2510/02C12N2740/15043
Inventor 万晓春李欣唐超刘绿艳
Owner SHENZHEN BINDEBIOTECH CO LTD
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