Single-chain antibody targeting HER2, chimeric antigen receptor T cell, 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 such as the lack of relevant research and limitations of a variety of HER2-positive solid tumors, and achieve tissue-specific expression and highly tissue-specific expression. expressive effect

CN109836501AInactive Publication Date: 2019-06-04SHENZHEN BINDEBIOTECH CO LTD
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Patent Information

Authority / Receiving Office
CN · China
Current Assignee / Owner
Publication Date
2019-06-04
Estimated Expiration
Not applicable · inactive patent

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Abstract

The present invention provides a single-chain antibody targeting HER2, the single-chain antibody targeting HER2 comprises an amino acid sequence shown in SEQ ID NO: 1. The present invention also provides a chimeric antigen receptor T cell comprising the single-chain antibody targeting HER2, wherein the chimeric antigen receptor targeting HER2 can specifically target HER2, the expansion of T cellsin patients is promoted, the tumor cells can be efficiently and specifically killed, the chimeric antigen receptor T cell has lasting cell viability and lethality, and damage is hardly generated on the normal cells. The invention also provides a preparation method and an application of the chimeric antigen receptor T cell targeting HER2.
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Description

technical field

[0001] The invention relates to the field of medical biology, in particular to a HER2-targeting single-chain antibody, a chimeric antigen receptor T cell, and a preparation method and application thereof. Background technique

[0002] The global incidence of breast cancer has been on the rise since the late 1970s, and breast cancer has become a major public health problem in the current society. Clinically, human epidermal growth factor receptor-2 (HER2) is an important prognostic factor for breast cancer, which is closely related to the spread and metastasis of breast cancer. HER2 is a member of the human epithelial growth factor receptor family. The HER2 gene product is normally expressed in secretory gland epithelial cells. When its gene copy increases abnormally, it will drive the malignant transformation and expansion of the cell. According to statistics, about 20-30% of breast cancer patients are HER2 positive. Compared with HER2-negative breast cance...

Examples

Embodiment 1

[0080] A method for preparing chimeric antigen receptor T cells targeting HER2, comprising the following steps:

[0081] (1) Prepare the gene sequence of chimeric antigen receptor CAR-HER2 targeting HER2

[0082] The coding genes of the signal peptide, the single-chain antibody targeting HER2, the CD8α hinge region, the CD8 transmembrane region, the 4-1BB signal region and the CD3ζ signal region are respectively prepared, and the coding genes of the signal peptide are shown in SEQ ID NO: 15 , the coding gene of the single-chain antibody targeting HER2 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: As shown in ID NO: 9, the gene encoding the 4-1BB signal region is shown in SEQ ID NO: 11, and the gene encoding the CD3ζ signal region is shown in SEQ ID NO: 13.

[0083] The genes encoding the above signal peptide, HER2-targeting single-chain antibody, CD8α hing...