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Pharmaceutical composition for treating tumors or cancers and application thereof

A composition and oncolytic technology, applied in the biological field, can solve the problems of not being able to make a drug alone, slow clearance, and low efficiency of rhein

Active Publication Date: 2020-11-17
FANTASIA BIOPHARMA ZHEJIANG CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Second, in vivo, viral replication is restricted over time and slowly cleared by the body
[0009] But for now, there are still places that need improvement in the prior art
Firstly, the overall treatment efficiency of rhein is not high. Secondly, currently, in tumors such as melanoma and colon cancer, the effective control rate of immunotherapy drugs used alone is about 10%, which is not a very high rate compared with traditional treatments. Response rate, not medicine alone

Method used

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  • Pharmaceutical composition for treating tumors or cancers and application thereof
  • Pharmaceutical composition for treating tumors or cancers and application thereof
  • Pharmaceutical composition for treating tumors or cancers and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0130] Example 1 Experimental scheme of rhein and virus U400 combined treatment of LLC-T2 unilateral tumor

[0131] The specific implementation process is as figure 1 As shown, the first 120 C57BL / 6 mice ordered, female, 18-20g, were inoculated with LLC-T2 (2x 10 5 ) tumor cells, grow the tumor volume to 100mm on Day 9-10 3 Left and right (80-120mm 3 ), 100 tumor-bearing mice were randomly divided into 4 groups, respectively PBS group, RH group, virus U400 group and combined treatment (RH+virus U400) group, RH was administered once every 4 days by intraperitoneal injection, a total of The drug was administered 3 times, and the virus U400 was administered once every 2 days by intratumoral injection, for a total of 3 times. During the experiment, the tumor body was measured once every 2 days. The mice were sacrificed, and the tumors were removed and weighed. After dissection, the lung tissues of the mice were taken to take fluorescence pictures of lung cancer cell metastas...

Embodiment 2

[0132] Embodiment 2 establishes subcutaneous transplantation lung cancer model, and compares the therapeutic effect of different mutant strain viruses in the treatment of subcutaneous transplantation tumor fruit

[0133] 40 C57BL / 6 mice, female, 18-20g, were inoculated with LLC-T2 (2.2x10 5 ) tumor cells, grow the tumor volume to 100mm on Day 9-10 3 left and right (80-120mm 3 ), the tumor-bearing mice were randomly divided into 5 groups, namely the PBS group, U000, U200, U500 and U400, and administered for 3 times in total. The virus was administered once every 2 days by intratumoral injection, and administered for 3 During the experiment, the tumor body was measured once every 2 days. On Day 29-30 of the experiment, all mice were sacrificed, and the tumor body was removed and weighed.

[0134] figure 2 A is the dosing regimen of OV oncolytic virus (intratumoral injection). As shown in the figure, when the tumor volume reaches 100mm 3 , by intratumoral injection of o...

Embodiment 3

[0137] Example 3 Comparison of the Effects of Different Mutant Viruses on Lung Metastasis of Lung Cancer

[0138] On Day0, LLC lung cancer cells (2x 10 5 / only) subcutaneous injection to establish mouse lung cancer xenograft tumor model, on Day 9, when the tumor volume reaches 100mm 3 At the left and right, the mice were randomly grouped, and different mutant strains of virus were administered by intratumoral injection. At the end of the experiment, all the lung tissues of the mice were collected. Since the red fluorescent protein was introduced into the LLC cells, they were examined under a 40-fold microscope. , take fluorescence pictures of lung metastases, and calculate the fluorescence ratio.

[0139] Experimental results such as image 3 shown. Specifically, as image 3 As shown in A, the lung metastasis rate of the mice in the PBS group was about 100%, while the rest of the treatment groups were significantly lower than the PBS group, and the completely transplante...

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PUM

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Abstract

The invention relates to a pharmaceutical composition for treating tumors or cancers and application thereof. Particularly, the pharmaceutical composition comprises an oncolytic rhabdovirus deliveredthrough direct local injection or systemic administration or intratumoral delivery, and the oncolytic rhabdovirus can generate a synergistic inhibition effect on tumors and / or cancers in combination with administration of a CD38 small-molecule inhibitor. Besides, the oncolytic rhabdovirus has the characteristic of recognizing tumor cells and cannot damage normal cells, meanwhile, the CD38 small-molecule inhibitor has the specific T cell receptor molecule inhibiting activity, and the safety and the curative effect are remarkably excellent through combined use of the oncolytic rhabdovirus and the CD38 small-molecule inhibitor.

Description

technical field [0001] The invention belongs to the field of biotechnology, and in particular relates to a pharmaceutical composition and its application in medicine for treating tumor or cancer. Background technique [0002] Malignant tumor is the main disease that causes human death, and the main treatment methods include surgery, radiotherapy and chemotherapy. Biological therapy is the fourth method developed in recent years and is known as the treatment of malignant tumors. It includes tumor vaccine therapy, tumor non-specific immunotherapy, antibody immunotherapy, cytokine therapy, adoptive cell immunotherapy, tumor gene therapy, etc. . Tumors arise from the accumulation of genetic and epigenetic changes in normal cells that drive the transformation of normal cells into malignancy. This complex pathological change process determines the diversity of mechanisms in the occurrence, maintenance and metastasis of different tumors. At present, surgical resection, chemother...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61K35/768A61K31/192A61P35/00A61P35/02
CPCA61K45/06A61K35/768A61K31/192A61P35/00A61P35/02A61K2300/00C12N7/00A61K31/122A61P35/04A61P11/00C07K14/005C12N2760/20222C12N2760/20232A61K35/766A61K38/162
Inventor 秦晓峰吴飞
Owner FANTASIA BIOPHARMA ZHEJIANG CO LTD
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