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Dual-signal independent chimeric antigen receptors (dsCAR) and uses thereof

A chimeric antigen receptor, dual-signal technology, applied in the direction of antibodies, antibody mimics/stents, medical preparations containing active ingredients, etc., can solve problems such as decreased therapeutic efficacy

Active Publication Date: 2014-01-01
SHANGHAI CELL THERAPY GRP CO LTD
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Problems solved by technology

However, CAR + The "cascade" effect caused by off-target T cells is very fast, and these suicide systems may not be able to function in time
Another approach is to reduce CAR + The number of T cells reinfused, this program will reduce the efficacy of treatment

Method used

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  • Dual-signal independent chimeric antigen receptors (dsCAR) and uses thereof
  • Dual-signal independent chimeric antigen receptors (dsCAR) and uses thereof
  • Dual-signal independent chimeric antigen receptors (dsCAR) and uses thereof

Examples

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Embodiment Construction

[0033] The term "chimeric antigen receptor" in the present invention is an artificially modified receptor that can anchor specific molecules (such as antibodies) that recognize tumor antigens to immune cells (such as T cells), allowing immune cells to recognize tumor antigens or viruses Antigens and kill tumor cells or virus-infected cells.

[0034] The term "T cell activation-related signal" in the present invention refers to the two signals required for T cell activation, that is, the combination of TCR-CD3 complex on the surface of T cells and antigen peptide-MHC molecules provides the first signal for T cell activation, which determines Killing specificity of T cells; co-stimulatory molecules (such as CD28) on the surface of T cells combine with corresponding ligands (such as B7) to provide a second signal for T cell activation and promote T cell activation, proliferation and survival.

[0035] In the present invention, the term "immunoreceptor tyrosine-based activation mo...

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Abstract

The invention relates to chimeric antigen receptors (CAR), particularly relates to dual-signal independent chimeric antigen receptors (dsCAR), and also relates to immune response cells of the dual-signal independent chimeric antigen receptors (dsCAR) and uses of the immune response cells in preparation of drugs for treatment of malignant tumor and virus infected diseases. In detail, the dual-signal independent chimeric antigen receptors (dsCAR) can respectively identify two different family antigens of tumor cells and can respectively transmit two T-cell-activation related signals. One of the CAR can transmit a first T-cell-activation related signal by combing a ligand of a tumor specific antigen or a tumor-associated antigen to decide T-cell killing specificity, and the other CAR can transmit a second T-cell-activation related signal by combing a ligand of a membrane receptor (such as EGFR (epidermal growth factor receptor) family protein) widely expressed by the tumor cells to promote T cell activation, proliferation and survival. The dual-signal independent chimeric antigen receptors (dsCAR) can avoid the potential safety problems on the basis of maintaining curative effects of second generation and third generation CAR.

Description

technical field [0001] The present invention relates to a chimeric antigen receptor, especially a dual-signal independent chimeric antigen receptor, the present invention also relates to an immune response cell expressing the chimeric antigen receptor, and the immune response cell is used for preparing a therapeutic Use in medicine for malignant tumors and viral infectious diseases. Background technique [0002] Adoptive cell therapy (ACT) is a method to reinfuse processed autologous or allogeneic immune cells (mainly autologous cells) to tumor patients to enhance the patient's immune function and achieve therapeutic purposes. Currently, tumor ACT is progressing rapidly, and adoptive immunotherapy using tumor-infiltrating lymphocytes (TIL) has achieved very good clinical effects on melanoma (Science 2002;298:850-4). However, T cell activation requires the stimulation of two signals, two T cell activation related signals. Among them, the TCR-CD3 complex on the surface of T ...

Claims

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Application Information

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IPC IPC(8): C07K19/00C12N5/10A61K48/00A61P31/12A61P35/00
CPCC07K2317/622A61K38/177C07K16/28A61K39/395C07K16/3092G01N33/48C07K2319/32A61K38/17C12N15/63C07K19/00C07K14/705A61P31/12A61P35/00C07K14/7051C07K14/7056C07K2319/00
Inventor 钱其军金华君丁娜俞德超李林芳吴孟超
Owner SHANGHAI CELL THERAPY GRP CO LTD
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