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A chimeric antigen receptor targeting HER2 and co-expressing PD1-mica fusion protein, its expression vector and application

A PD1-MICA, chimeric antigen receptor technology, applied in the field of tumor immune drugs, can solve problems such as ineffectiveness

Active Publication Date: 2021-08-10
华夏源细胞工程集团股份有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, although CAR-T cells can effectively kill HER2-positive tumor cells in vitro, traditional CAR-T cells are almost ineffective in vivo due to the influence of the tumor microenvironment

Method used

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  • A chimeric antigen receptor targeting HER2 and co-expressing PD1-mica fusion protein, its expression vector and application
  • A chimeric antigen receptor targeting HER2 and co-expressing PD1-mica fusion protein, its expression vector and application
  • A chimeric antigen receptor targeting HER2 and co-expressing PD1-mica fusion protein, its expression vector and application

Examples

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Embodiment 1

[0026] The embodiment of the present invention provides a chimeric antigen receptor targeting HER2 and co-expressing PD1-MICA fusion protein, such as figure 1 As shown, the chimeric antigen receptor includes: sequentially connected signal peptide (human CD8α signal peptide, CD8α leader), single-chain antibody targeting HER2 (HER2 scFv), elongated CD8α hinge region (human CD8α hinge region, CD8α Hinge), transmembrane region (human CD8α transmembrane region, CD8α transmembrane), co-stimulatory factor, intracellular signal peptide (human CD3ζ intracellular signal peptide, CD3ζsignal), P2A connecting peptide, IL2 signal peptide, PD1 extracellular region and MICA The extracellular region, the nucleotide sequence of the signal peptide is shown in SEQ ID NO:1 in the sequence listing, the nucleotide sequence of the single-chain antibody targeting HER2 is shown in SEQ ID NO:2 in the sequence listing, and the lengthened CD8α The nucleotide sequence of the hinge region is shown in SEQ ID...

Embodiment 2

[0034] The present invention provides an expression vector, which includes the vector and the chimeric antigen receptor provided in Example 1. The vector can be a lentiviral vector.

[0035] The following briefly introduces the preparation method of the expression vector, as follows:

[0036] PCR (Polymerase Chain Reaction, Polymerase Chain Reaction) amplifies and obtains the CAR01 gene sequence, and adds restriction site Xba I and restriction site EcoR I to the two ends of the CAR01 gene sequence to obtain the product to be digested, Carry out the double digestion reaction of Xba I and EcoR I with the lentiviral vector plasmid pCDH-EF1-MCS-T2A-copGFP, respectively, to obtain the digestion fragment containing CAR01 and the digestion fragment containing ppCDH-EF1-MCS-T2A-copGFP fragment. The enzyme digestion reaction conditions are as follows: the enzyme digestion temperature is 37° C., and the enzyme digestion time is 30 min. Enzyme digestion system (total volume 50 μL) inc...

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Abstract

The invention discloses a chimeric antigen receptor targeting HER2 and co-expressing PD1-MICA fusion protein as well as its expression vector and application, which belong to the field of tumor immunity drugs. The chimeric antigen receptor includes: sequentially linked signal peptide, single-chain antibody targeting HER2, CD8α hinge region and transmembrane region, co-stimulatory factor, intracellular signal peptide, P2A linking peptide, IL2 signal peptide, PD1 cell Extracellular domain and MICA extracellular domain. The chimeric antigen receptor secretes PD1-MICA fusion protein while specifically targeting HER2-positive tumor cells, targets PD-L1 / PD-L2 positive tumor cells, and blocks PD1 and PD-L1 / PD-L1 of T cells L2 inhibits the signal, and at the same time, the extracellular region of MICA can bind to the NKG2D receptor to activate NK cells, so as to realize the purpose of CAR-T cells to effectively kill HER2-positive tumor cells in vivo.

Description

technical field [0001] The invention relates to the field of tumor immunity drugs, in particular to a chimeric antigen receptor targeting HER2 and co-expressing PD1-MICA fusion protein, its expression vector and application. Background technique [0002] Malignant tumors are one of the diseases that seriously threaten human health. According to incomplete statistics, the annual incidence of malignant tumors in China has reached more than 4 million cases. In addition, studies in recent years have shown that the incidence of tumors has continued to increase, and the age of onset has also advanced. The disease population has gradually spread to young patients from the past, which is mostly middle-aged and elderly. , unhealthy living habits and other factors. Breast cancer is one of the most common malignant tumors affecting women's health. Patients with HER2-positive breast cancer account for 15% to 30% of the total number of breast cancer patients. This HER2-positive breast c...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K19/00C12N15/867A61K39/00A61P35/00
CPCA61P35/00A61K39/001106A61K2039/812C07K14/7051C07K14/70521C07K14/70539C07K16/32C07K2317/622C07K2319/02C07K2319/03C07K2319/33C12N15/86C12N2740/15043
Inventor 张坤
Owner 华夏源细胞工程集团股份有限公司
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