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Application of VEGF antibody and ANG2 antibody in preparation of drug for treating tumor with Ras mutation

A technology of antibodies and drugs, applied in the field of medical drugs, can solve problems such as limiting the application of anti-VEGF antibodies, and achieve the effect of improving the therapeutic effect

Pending Publication Date: 2021-01-05
义慧科技(深圳)有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] However, in the actual clinical process, anti-VEGF antibodies and anti-ANG2 antibodies do not work on every tumor that highly expresses VEGF or ANG2, and some tumors will develop resistance to anti-VEGF antibodies and anti-ANG2 antibodies, so some The resistance of some tumors to anti-VEGF antibodies and anti-ANG2 antibodies also limits the application of anti-VEGF antibodies

Method used

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  • Application of VEGF antibody and ANG2 antibody in preparation of drug for treating tumor with Ras mutation
  • Application of VEGF antibody and ANG2 antibody in preparation of drug for treating tumor with Ras mutation
  • Application of VEGF antibody and ANG2 antibody in preparation of drug for treating tumor with Ras mutation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] T241 tumor cells and T241-Kras tumor cells with RAS mutation introduced are provided. Cells were placed in 10% FBS-DMEM (catalog number SH30243. 01, HyClone) culture medium.

[0040] The animal experiments of the present application used male C57B1 / 6 mice aged 6-8 weeks, maintained the mice under standard animal feeding conditions, and fed a standard diet. 1 × 10 suspended in 30 μL, PBS 6 T241 tumor cells, and 1×10 suspended in 30 μL, PBS 6 Two T241-Kras tumor cells were subcutaneously implanted into different C57Bl / 6 mice. Tumor size was measured with calipers every other day, and the volume of T241 tumors transplanted subcutaneously was calculated according to standard formulas.

[0041] When the tumor reaches a certain size, the 5mg / kg rabbit anti-mouse monoclonal VEGF-specific neutralizing antibody (product number BD0801, provided by Simcere Pharmaceutical Company (Nanjing, Jiangsu, China)) is used as the anti-VEGF antibody used in this application. A subset of...

Embodiment 2

[0044] MC38 tumor cells and MC38-Kras tumor cells with RAS mutation introduced are provided. The murine MC38 colon cancer cell line in this application was kindly provided by Dr. Rubén Hernández, Department of Gene Therapy, Center for Applied Medical Research, University of Navarre, Pamplona, ​​Navarra, Spain. The same subcutaneous transplantation and drug administration experiments as in Example 1 were carried out, and after a certain period of time, the mice were examined. The result is as Figure 2A and Figure 2B shown.

[0045] Figure 2A It is the result graph of tumor volume in mice after transplantation of MC38 tumor cells, Figure 2B It is the result graph of tumor volume of mice after transplantation of MC38-Kras tumor cells, VT represents the result of tumor volume after injection of non-immune rabbit IgG, Anti-VEGF represents the result of tumor volume after injection of anti-VEGF antibody, Anti-ANG2 represents the result of injection of anti-ANG2 The result o...

Embodiment 3

[0047] Provide A549 tumor cells (containing RAS mutation), carry out the same subcutaneous transplantation and administration experiments as in Example 1, after a certain period of time, the mice are checked, the results are as follows image 3 shown. image 3 It is the result graph of tumor volume of mice after transplanting A549 tumor cells, VT represents the result of tumor volume after injection of non-immune rabbit IgG, Anti-VEGF represents the result of tumor volume after injection of anti-VEGF antibody, Anti-ANG2 represents the result of injection of anti-ANG2 antibody The tumor volume results of Anti-VEGF+Anti-ANG2 indicate the tumor volume results after injection of anti-VEGF antibody and anti-ANG2 antibody. image 3 Among them, anti-VEGF antibody and anti-ANG2 antibody alone do not have the effect of inhibiting tumor volume, but they can effectively inhibit tumor volume and the effect is obvious when used in combination.

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Abstract

The invention provides application of a VEGF antibody and an ANG2 antibody in preparation of a drug for treating a tumor with Ras mutation. The VEGF antibody and the ANG2 antibody are used jointly, and thus, the treatment effect on the tumor with the Ras mutation can be effectively improved. The invention further provides a pharmaceutical composition. The drug for treating the tumor with the Ras mutation comprises the VEGF antibody and the ANG2 antibody.

Description

technical field [0001] The invention relates to the technical field of medical medicine, in particular to the application of anti-VEGF antibody and anti-ANG2 antibody in the preparation of drugs for treating tumors with Ras mutation. Background technique [0002] Vascular endothelial growth factor (VEGF) induces angiogenesis in vivo. The process of angiogenesis plays an important role in the growth and metastasis of tumors. Since VEGF plays an important regulatory role in angiogenesis, VEGF can be secreted in large quantities inside and outside tumor tissues; and the expression of VEGF is up-regulated in most malignant tumors . Angiopoietin (ANG) is highly expressed in various tumors such as prostate cancer, breast cancer, lung cancer, and liver cancer, and its mechanism involves affecting cell apoptosis signaling pathways and stimulating rRNA transcription. Among them, ANG2 promotes tumor growth by destabilizing blood vessels. Angiogenesis and growth. Therefore, it is of...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61P35/00
CPCC07K16/22A61P35/00C07K2317/73
Inventor 杨云龙曹义海
Owner 义慧科技(深圳)有限公司