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Medical application of DNA methyltransferase inhibitor in combination with anti-CD47 antibody for preparing antineoplastic drugs

A technology of methyltransferase and inhibitors, which is applied in the field of medical applications for the preparation of anti-tumor drugs, and can solve the problems of DNA methyltransferase inhibitors and anti-CD47 antibodies that have not yet been seen

Active Publication Date: 2019-01-18
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] There is no report on the combination of DNA methyltransferase inhibitors and anti-CD47 antibodies for anti-tumor

Method used

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  • Medical application of DNA methyltransferase inhibitor in combination with anti-CD47 antibody for preparing antineoplastic drugs
  • Medical application of DNA methyltransferase inhibitor in combination with anti-CD47 antibody for preparing antineoplastic drugs
  • Medical application of DNA methyltransferase inhibitor in combination with anti-CD47 antibody for preparing antineoplastic drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Example 1: DNA methyltransferase inhibitor 5-azacytidine and anti-CD47 antibody for the treatment of melanoma

[0024] 1. Experimental materials

[0025] The experimental animals are clean-grade male C57BL / 6 mice, weighing 18-20 g. The tumor cell line is B16-F10 melanoma, cultured in DMEM containing 10% fetal bovine serum at 37°C, 5% CO 2 cultivated under conditions.

[0026] 5-azacytidine was purchased from Ron Reagents (CAS No.: 320-67-2), anti-CD47 antibody was purchased from BioXcell (Lot: 670618M2), and diluted with normal saline or PBS when used.

[0027] Fetal bovine serum and DMEM medium are GIBCO products.

[0028] 2. Experimental method

[0029] 1. Modeling and grouping of transplanted tumor models

[0030] Take the tumor cells in the logarithmic growth phase, discard the original medium, wash with PBS, then add trypsin to digest until the wall is detached, discard the trypsin, add fresh medium and blow gently, transfer the cells to a centrifuge tube, Ce...

Embodiment 2

[0053] Example 2: DNA methyltransferase inhibitor 5-azacytidine and anti-CD47 antibody for the treatment of lung cancer

[0054] 1. Experimental materials

[0055] The experimental animals are clean-grade male C57BL / 6 mice, weighing 18-20 g. The tumor cell line is A549 lung cancer cells, cultured in DMEM containing 10% fetal bovine serum at 37°C, 5% CO 2 cultivated under conditions.

[0056] 5-azacytidine was purchased from Ron Reagents (CAS No.: 320-67-2), anti-CD47 antibody was purchased from BioXcell (Lot: 670618M2), and diluted with normal saline or PBS when used.

[0057] Fetal bovine serum and DMEM medium are GIBCO products.

[0058] 2. Experimental method

[0059] 1. Modeling and grouping of transplanted tumor models

[0060] Take the tumor cells in the logarithmic growth phase, discard the original medium, wash with PBS, then add trypsin to digest until the wall is detached, discard the trypsin, add fresh medium and blow gently, transfer the cells to a centrifuge tu...

Embodiment 3

[0083] Example 3: DNA methyltransferase inhibitor decitabine and anti-CD47 antibody are used to treat leukemia

[0084] 1. Experimental materials

[0085] The experimental animals are clean-grade male C57BL / 6 mice, weighing 18-20 g. The tumor cell line is L1210 leukemia cells, cultured with RPMI 1640 containing 10% fetal bovine serum at 37°C, 5% CO 2 cultivated under conditions.

[0086] Decitabine was purchased from Ron Reagent Company (CAS No.: 2353-33-5), anti-CD47 antibody was purchased from BioXcell (Lot: 670618M2), and diluted with normal saline or PBS when used.

[0087] Fetal bovine serum and RPMI 1640 medium are products of GIBCO.

[0088] 2. Experimental method

[0089] 1. Modeling and grouping of transplanted tumor models

[0090] Take the tumor cells in the logarithmic growth phase, discard the original medium, wash with PBS, then add trypsin to digest until the wall is detached, discard the trypsin, add fresh medium and blow gently, transfer the cells to a ce...

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Abstract

The invention discloses a medical application of DNA methyltransferase inhibitor combined with anti-CD47 antibody for preparing antineoplastic drugs, which will be appreciated by those skilled in theart, CD47 in physiological state can maintain the immune tolerance of the body's own cells, and in pathological state, it can be overexpressed in a variety of hematological tumors and solid tumors, through the combination of phagocyte ligands to initiate a series of inhibitory signal transduction to avoid phagocytosis, and inhibit the presentation of tumor antigens phagocytes, anti-CD47 antibody has anti-tumor effect. However, anti-CD47 antibodies alone are expensive and have limited efficacy. DNA methyltransferase inhibitors play an anti-tumor role by restoring the activity of tumor suppressor genes. As that DNA methyltransferase inhibitor and the anti-CD47 antibody combine to exhibit obvious synergistic effect on anti-tumor, the DNA methyltransferase inhibitor and the anti-CD47 antibodycan be combined to be use for anti-tumor, thereby enhancing the anti-tumor effect of the anti-CD47 antibody and reducing the economic burden of the patient.

Description

technical field [0001] The invention belongs to the field of medicine, and relates to the combined administration of antitumor drugs, in particular to the medical application of DNA methyltransferase inhibitors and anti-CD47 antibodies in combination for the preparation of antitumor drugs. Background technique [0002] Immune escape is an important behavioral feature of tumor cells, and one of its mechanisms is the high expression of immunosuppressive signals. At present, drugs targeting immunosuppressive signals such as CTLA-4, PD1 and other targets have been marketed, and have shown significant anti-tumor effects, but they all target the specific immunity of T cells. CD47 is a "don't eat me" signal. Under physiological conditions, it can maintain the immune tolerance of the body's own cells. Under pathological conditions, it can be highly expressed on a variety of blood tumors and solid tumors. The binding of the upper ligand initiates a series of inhibitory signal transd...

Claims

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Application Information

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IPC IPC(8): A61K45/06A61K39/395A61P35/00A61P35/02A61K31/7068A61K31/706
CPCA61K31/706A61K31/7068A61K39/395A61K45/06A61P35/00A61P35/02A61K2300/00
Inventor 杨华李萍刘莲吴循循
Owner CHINA PHARM UNIV
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