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Human chimeric antigen receptor for treating hematological neoplasms, and application of human chimeric antigen receptor

A chimeric antigen receptor, human-derived technology, applied in the direction of targeted specific cell fusion, medical raw materials derived from mammals, anti-tumor drugs, etc., can solve the problem of relapse, affect the long-term survival of CAR-T cells, etc. question

Active Publication Date: 2019-01-25
WUHAN BIO RAID BIOTECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, chimeric antigen receptors targeting CD30 mostly use murine scFv, which is immunogenic, and the body will produce human anti-mouse antibodies, which affects the long-term survival of CAR-T cells in the body and easily causes recurrence

Method used

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  • Human chimeric antigen receptor for treating hematological neoplasms, and application of human chimeric antigen receptor
  • Human chimeric antigen receptor for treating hematological neoplasms, and application of human chimeric antigen receptor
  • Human chimeric antigen receptor for treating hematological neoplasms, and application of human chimeric antigen receptor

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Embodiment Construction

[0018] The principles and features of the present invention are described below in conjunction with the examples and accompanying drawings. The examples are only used to explain the present invention and are not intended to limit the scope of the present invention.

[0019] 1. Construction of Human-derived Chimeric Antigen Receptor Expression Plasmid Targeting CD30

[0020] By artificially synthesizing a 1614bp DNA fragment (the nucleic acid sequence of hCD30CAR) shown in SEQ ID NO: 7, wherein the 1-69 nucleotides encode SP (the amino acid sequence of which is shown in SEQ ID NO: 2) , the 70-798th nucleotides encode human-derived CD30-targeting SCFV (the amino acid sequence is shown in SEQ ID NO: 3), the 799-945th nucleotides encode the CD8 hinge region (the amino acid sequence is as shown in Shown in SEQ ID NO:4), the 946-1026 nucleotide encoding CD28TM (its amino acid sequence is shown in SEQ ID NO:5), the 1027-1149 nucleotide encoding CD28ICD, the 1150-1215 The nucleotides...

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Abstract

The invention relates to a human chimeric antigen receptor for treating hematological neoplasms, and application of the human chimeric antigen receptor. The human chimeric antigen receptor comprises ahuman anti-CD30 single-chain antibody, an extracellular hinge region, a transmembrane domain and an intracellular signal domain, wherein the amino acid sequence of the human anti-CD30 single-chain antibody is shown in SEQ ID NO. 3. The invention also relates to nucleic acid for encoding the chimeric antigen receptor. Chimeric antigen receptor-T (CAR-T) cells can be obtained by transducing T cellsinto a chimeric antigen receptor-loaded lentiviral vector, so that CD30-positive tumor cells can be efficiently and specifically killed; therefore, the invention provides a method which is more efficient and less in side effects and adverse effects and can be used for treating CD30 surface antigen-positive malignant tumors such as hodgkin lymphoma.

Description

technical field [0001] The present invention relates to the field of cellular immunotherapy, and more particularly relates to a human chimeric antigen receptor for treating hematological tumors, including its coding sequence and application. Background technique [0002] CD30 is a member of the tumor necrosis factor receptor superfamily (tumor necrosis factor receptor superfamily, TNFRSF), which belongs to type I transmembrane glycoprotein, and is highly expressed in Hodgkin lymphoma (Hodgkinlymphoma, HL) and anaplastic large cell lymphoma ( Anaplastic large cell lymphomas, ALCL), low expression on the surface of activated T cells and B cells in non-pathological state, but not on normal cells. Early studies have shown that CD30 is involved in cell activation and differentiation, the conduction of NF-κB and other signals, and T cell immune activation. Current studies have confirmed that CD30 is closely related to cell proliferation and death, and its intracellular part can i...

Claims

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Application Information

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IPC IPC(8): C07K19/00C12N15/62C12N5/10A61K35/17A61P35/00
CPCA61K35/17A61P35/00C07K14/7051C07K16/2878C07K2317/622C07K2319/33C12N2510/00
Inventor 张同存顾潮江吴寒李杰珍舒冲牛敏杰许婧王芳
Owner WUHAN BIO RAID BIOTECH CO LTD
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