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Use of active substances for reducing activity or expression quantity of CXCL13 protein in preparing medicines for treating malignant tumor metastasis

A technology of active substances and protein activity, which is applied in antineoplastic drugs, gene therapy, drug combinations, etc.

Active Publication Date: 2018-05-29
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] In recent years, targeted therapy against T cell immune negative regulators based on PD-1 and CTLA-4 has made progress in the treatment of some tumors, but there is still room for improvement in the therapeutic effect

Method used

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  • Use of active substances for reducing activity or expression quantity of CXCL13 protein in preparing medicines for treating malignant tumor metastasis
  • Use of active substances for reducing activity or expression quantity of CXCL13 protein in preparing medicines for treating malignant tumor metastasis
  • Use of active substances for reducing activity or expression quantity of CXCL13 protein in preparing medicines for treating malignant tumor metastasis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0112] Embodiment 1. Experimental lung metastasis experiment of melanoma

[0113] 1. Tumor cell culture and establishment of metastatic tumor model:

[0114] (1) Melanoma B16 cells are cultured in DMEM medium (containing 10% fetal bovine serum). When the cells grow to about 50-70% in the plate, digest with trypsin at 37°C for about 2 minutes, neutralize the medium and pipette the remaining paste Parietal cells were transferred to a 15 ml conical centrifuge tube, centrifuged at 1500 rpm for 3 minutes, and the supernatant was discarded.

[0115] (2) The cells were resuspended and washed in serum-free DMEM medium, and centrifuged at 1500 rpm for 3 minutes. repeat.

[0116] (3) Count cells, resuspend concentration 1*10 6 / mL, each mouse was given 2*10 5 individual tumor cells, 200 μL.

[0117] (4) The mice were killed by neck dislocation 14 days or 21 days after inoculation of tumor cells, the chest cavity was opened to take out the lungs, and the blood clots were washed away...

Embodiment 2

[0157] Embodiment 2. Experimental Lung Metastasis Experiment of Lewis Lung Cancer

[0158] 1. Tumor cell culture and establishment of metastatic tumor model:

[0159] (1) Lewis lung cancer LL2 cells are cultured in DMEM medium (containing 10% fetal bovine serum). When the cells grow to about 50-70% in the plate, digest with trypsin at 37°C for about 1 minute, neutralize the medium, and pipette the remaining paste Parietal cells were transferred to a 15 ml conical centrifuge tube, centrifuged at 1500 rpm for 3 minutes, and the supernatant was discarded.

[0160] (2) The cells were resuspended and washed in serum-free DMEM medium, and centrifuged at 1500 rpm for 3 minutes. repeat.

[0161] (3) Count cells, resuspend concentration 1*10 6 / mL, each mouse was given 2*10 5 individual tumor cells, 200 μL.

[0162] 21 days after the inoculation of tumor cells, the mice were killed by neck dislocation, the chest was opened to take out the lungs, and the blood clots were washed awa...

Embodiment 3

[0166] Example 3. Lewis lung cancer spontaneous lung metastasis experiment

[0167] 1. Tumor cell culture and spontaneous metastasis model establishment:

[0168] (1) Lewis lung cancer LL2 cells are cultured in DMEM medium (containing 10% fetal bovine serum). When the cells grow to about 50-70% in the plate, digest with trypsin at 37°C for about 1 minute, neutralize the medium, and pipette the remaining paste Parietal cells were transferred to a 15 ml conical centrifuge tube, centrifuged at 1500 rpm for 3 minutes, and the supernatant was discarded.

[0169] (2) The cells were resuspended and washed in serum-free DMEM medium, and centrifuged at 1500 rpm for 3 minutes. repeat.

[0170] (3) Count cells, resuspend concentration 1*10 7 / mL, each mouse subcutaneously administered 1*10 6 individual tumor cells, 100 μL.

[0171] (4) 14 days after tumor cell inoculation, the subcutaneous tumor was surgically removed.

[0172] (5) Eleven days after surgical removal of the subcutan...

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Abstract

The invention belongs to the field of medicines, and particularly relates to use of active substances such as an antibody protein, a nucleic acid sequence and a small molecule inhibitor for reducing the activity or expression quantity of CXCL13 protein in preparing medicines for treating malignant tumor metastasis. The technical problem to be solved is to provide a targeted therapeutic solution for immunoregulatory molecules of B cells. The targeted therapeutic solution is to provide the use of the active substances for reducing the activity or expression quantity of the CXCL13 protein in preparing the medicines for treating the malignant tumor metastasis. Experiments show that a CXCL13 blocking agent or blocking antibody can significantly inhibit the lung metastasis of malignant tumors; and by combination of the CXCL13 blocking agent or blocking antibody with chemotherapeutics or T cell immune negative regulators, the inhibition on the lung metastasis of the malignant tumors is particularly effective, and a better synergic effect can be obtained. A new and effective choice for the treatment of the malignant tumor metastasis is provided.

Description

technical field [0001] The invention belongs to the field of tumor immunotherapy, and specifically relates to the use of an active substance reducing the activity or expression of CXCL13 protein in the preparation of a drug for treating malignant tumor metastasis. Background technique [0002] Invasion and metastasis are the most life-threatening biological characteristics of malignant tumors, and metastasis behavior is one of the most important characteristics that distinguish malignant tumors from benign tumors. Metastasis refers to the whole process in which malignant tumor cells break away from their primary site, transport in various ways in the body, reach a tissue discontinuous with the primary site, continue to proliferate and grow, and form a secondary tumor with the same pathological properties as the primary tumor . The emergence of metastasis marks a key turning point in the development of tumors. Once distant metastasis occurs, it often means that the tumor has...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K45/06A61K48/00A61P35/04
CPCA61K45/00A61K45/06A61K48/00
Inventor 魏于全任骏
Owner SICHUAN UNIV
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