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Application of engineered T cell with immune receptor for treatment of cancer

A technology of immune receptors and cells, applied in the field of immune cells, T cells modified by genetic engineering, and compositions for treating human cancer, can solve the problems of unsatisfactory curative effect

Inactive Publication Date: 2019-05-10
NANJING CART MEDICAL TECH LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Adoptive immunotherapy based on T lymphocytes has achieved certain effects in some tumors, and this immunotherapy method can overcome the defects of antibody therapy, but the efficacy in most tumors is still unsatisfactory [Grupp SA, et al .Adoptive cellular therapy.Curr Top Microbiol Immunol.,.2011;344:149-72.]

Method used

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  • Application of engineered T cell with immune receptor for treatment of cancer
  • Application of engineered T cell with immune receptor for treatment of cancer
  • Application of engineered T cell with immune receptor for treatment of cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Embodiment 1, chimeric antigen receptor preparation

[0042] The present invention provides a novel chimeric antigen receptor. The chimeric antigen receptor of the present invention is composed of the second intracellular conduction domain-T2A-extracellular signal peptide-antigen binding domain-the first intracellular conduction domain in series. Therefore, viral vectors containing different combinations of stimulation signals need to be constructed separately. In this example, the single-chain antibody targeting CD19 is used as the unified extracellular antigen recognition structure, and the following chimeric antigen receptors need to be constructed respectively:

[0043] DAP12-T2A-CD8α signal peptide-CD19 antigen-binding domain-NKp46 (CAR1)

[0044] DAP12-T2A-CD8α signal peptide-CD19 antigen-binding domain-NKp30 (CAR2)

[0045] DAP12-T2A-CD8α signal peptide-CD19 antigen-binding domain-NKp44 (CAR3)

[0046] DAP12-T2A-CD8α Signal Peptide-CD19 Antigen Binding Domain...

Embodiment 2

[0107] Embodiment 2, virus infection T cell

[0108] 1. Isolation and activation of T cells and virus infection

[0109] (1) Isolation of human peripheral blood mononuclear cells

[0110] Use a blood collection tube containing anticoagulant to collect about 10ml of peripheral blood, settle naturally at room temperature (18-25°C) for about 30min, collect the upper layer of plasma, and centrifuge the collected upper layer of plasma at 5000r / min for 10min at a volume ratio of 1:1 Add to the lymphocyte separation medium (purchased from Tianjin Haoyang Biological Products Technology Co., Ltd.), gradient centrifugation, 3000r / min, centrifugation for 30min, after centrifugation, the centrifuge tube is layered from top to bottom: the first layer is the plasma layer ; The second layer is the buffy coat layer of lymphocytes; the third layer is the transparent separation liquid layer; the fourth layer is the red blood cell layer. Aspirate the buffy coat of lymphocytes, wash twice with ...

Embodiment 3

[0115] Example 3. Effect of Virus Infection of CAR-T Cells on Cell Proliferation

[0116] After each group of viruses infected T cells, the T cells were counted every 1-2 days with a complete medium containing 5% autologous plasma + 300 IU / ml recombinant human IL-2 + KBM581. Then observe the growth of T lymphocytes, the results are as follows: figure 2 shown. The results showed that after the cells were infected with CAR-expressing viruses, they could still form a typical proliferating clonal group. By counting the cells and drawing the cell proliferation curve, it can be seen that the proliferation of CAR1-CAR24 was similar, and compared with T cells not infected with the virus ( figure 2 Medium NTD) proliferative ability was slightly weaker.

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Abstract

The invention discloses application of an engineered T cell with an immune receptor for treatment of cancer. A chimeric antigen receptor consists of an extracellular signal peptide, an antigen bindingstructural domain, a first intracellular conduction structural domain and a second intracellular conduction structural domain and comprises the first intracellular conduction structural domain in theform of the immune receptor. The invention provides a plurality of amino acid sequences of the chimeric antigen receptor and provides the chimeric antigen receptor specific for CD19 malignant hematological tumors and CAR-T cells. In a blood tumor killing test, the ability of the CAR-T cells to kill tumor cells is significantly improved, and high safety and high antitumor activity are shown in clinical application.

Description

technical field [0001] The invention relates to the technical field of tumor immunotherapy, and provides a composition and a method for treating human cancer. The present invention involves T cells genetically engineered to express a CAR, wherein the CAR includes an antigen binding domain, a first transduction domain and a second transduction domain. The present invention also relates to vectors encoding such transmembrane polypeptides, and immune cells expressing said CAR on their surface for immunotherapy. The present invention opens the way to an effective adoptive immunotherapy strategy for the treatment of cancer. Background technique [0002] With the development of tumor immunology theory and clinical technology, chimeric antigen receptor T-cell immunotherapy (CAR-T) has become one of the most promising tumor immunotherapy [Schmitz M, et al . Chimeric antigen receptor-engineered T cells for immunotherapy of Cancer. J Biomed Biotechnol, 2010, doi: 10.1155 / 2010 / 956304...

Claims

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Application Information

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IPC IPC(8): C07K19/00C12N5/10C12N15/867A61K35/17A61P35/00
Inventor 王恩秀汪晨张海
Owner NANJING CART MEDICAL TECH LTD
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