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Chimeric antigen receptor targeting GPC3 and application of chimeric antigen receptor

A chimeric antigen receptor and targeting technology, applied in the field of chimeric antigen receptor targeting GPC3, can solve the problems of not achieving good curative effect, lack of tumor-specific antigen, etc., achieving good application prospects and strong anti-entity Tumor activity and volume reduction effect

Active Publication Date: 2020-01-14
华夏源细胞工程集团股份有限公司
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, in terms of the application of solid tumors, due to the lack of tumor-specific antigens and other reasons, CAR-T has not yet achieved good clinical efficacy in the treatment of solid tumors.

Method used

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  • Chimeric antigen receptor targeting GPC3 and application of chimeric antigen receptor
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  • Chimeric antigen receptor targeting GPC3 and application of chimeric antigen receptor

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Embodiment

[0020] An embodiment of the present invention provides a chimeric antigen receptor targeting GPC3, the chimeric antigen receptor comprising: sequentially connected signal peptide, single-chain antibody targeting GPC3 (Glypican-3), Myc tag, CD8α hinge region, CD28 transmembrane region, co-stimulatory factor, intracellular signal domain, P2A connecting peptide and CCL19 secretory region, the nucleotide sequence of the signal peptide is shown in SEQ ID NO: 1 in the sequence listing, and the targeting GPC3 The nucleotide sequence of the single-chain antibody is shown in SEQ ID NO: 2 in the sequence listing, the nucleotide sequence of the Myc tag is shown in SEQ ID NO: 3 in the sequence listing, and the nucleotide sequence of the CD8α hinge region The acid sequence is shown in SEQ ID NO: 4 in the sequence listing, the nucleotide sequence of the CD28 transmembrane region is shown in SEQ ID NO: 5 in the sequence listing, and the nucleotide sequence of the intracellular signal domain i...

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Abstract

The present invention discloses a chimeric antigen receptor targeting GPC3 and an application of the chimeric antigen receptor, and belongs to the field of tumor immunotherapy. The chimeric antigen receptor comprises a signal peptide, a single-chain antibody targeting GPC3, a Myc tag, a CD8-alpha hinge region, a CD28 transmembrane region, a co-stimulatory factor, an intracellular signal domain, aP2A linker peptide and a CCL19 secretion region connected in sequence. The chimeric antigen receptor can recognize GPC3 antigen, CAR-T cells constructed by using the novel chimeric antigen receptor have good killing ability for GPC3 target proteins, at the same time, the chimeric antigen receptor targeting the GPC3 can also secrete chemokine CCL19, the produced chemokine is expected to promote infiltration of immune cells into tumor microenvironment without changing antitumor activity, inhibits growth rate of tumors, and reduces volume of the tumors, so that the chimeric antigen receptor targeting the GPC3 has stronger anti-solid tumor activity and thus shows good application prospects.

Description

technical field [0001] The invention relates to the field of tumor immunotherapy, in particular to a chimeric antigen receptor targeting GPC3 and its application. Background technique [0002] Chimeric Antigen Receptor T-Cell (CAR-T) is constructed by introducing a CAR gene fused into the host T lymphocyte genome in the form of nucleic acid. The application of CAR-T in hematological tumors has shown gratifying therapeutic effects, especially for relapsed and refractory B-lymphoblastic leukemia patients, with a remission rate of over 90%. However, in terms of the application of solid tumors, due to the lack of tumor-specific antigens and other reasons, CAR-T has not yet achieved good clinical efficacy in the treatment of solid tumors. Contents of the invention [0003] In order to solve the problems of the prior art, an embodiment of the present invention provides a chimeric antigen receptor targeting GPC3 and its application. Described technical scheme is as follows: ...

Claims

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Application Information

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IPC IPC(8): C07K19/00C12N15/62A61K39/00A61P35/00
CPCC07K16/303C07K14/7051C07K14/70517C07K14/70521C07K14/521A61K39/001142A61P35/00C07K2317/622C07K2319/02C07K2319/03C07K2319/41C07K2319/33C07K2319/74A61K2039/844A61K2039/86A61K2039/828A61K2039/812A61K2039/876A61K2039/892A61K2039/80
Inventor 张坤
Owner 华夏源细胞工程集团股份有限公司
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