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Use of oncolytic virus VG161 or combination of oncolytic virus VG161, gemcitabine and albumin paclitaxel in preparation of drugs for treating pancreatic cancer

A technology of VG161 and oncolytic virus, which is applied in the field of combination of gemcitabine and albumin-paclitaxel in the preparation of drugs for the treatment of pancreatic cancer, can solve the problems such as the application of oncolytic virus that has not been reported in the literature, and achieves increased therapeutic effect, less toxic and side effects, and pharmacological effects. clear effect

Pending Publication Date: 2021-06-18
THE FIRST AFFILIATED HOSPITAL ZHEJIANG UNIV COLLEGE OF MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0012] At present, there is no literature reporting the application of oncolytic virus combined with GEM+Nab-PTX regimen in pancreatic cancer

Method used

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  • Use of oncolytic virus VG161 or combination of oncolytic virus VG161, gemcitabine and albumin paclitaxel in preparation of drugs for treating pancreatic cancer
  • Use of oncolytic virus VG161 or combination of oncolytic virus VG161, gemcitabine and albumin paclitaxel in preparation of drugs for treating pancreatic cancer
  • Use of oncolytic virus VG161 or combination of oncolytic virus VG161, gemcitabine and albumin paclitaxel in preparation of drugs for treating pancreatic cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1VG161

[0036] Example 1 VG161 effectively kills pancreatic cancer cells in vitro and promotes apoptosis

[0037] 1. Cell killing and apoptosis-promoting experiments in vitro

[0038] In vitro experiments confirmed that VG161 single drug can kill and promote apoptosis of pancreatic cancer cell lines, which was detected by CCK8 and cell flow assay.

[0039] CCK8 is Cell Counting Kit-8, which can be used for easy and accurate cell proliferation and toxicity analysis. The basic principle is: the reagent contains WST-8 [chemical name: 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4 -disulfonic acid benzene)-2H-tetrazole monosodium salt], it is in the cell under the effect of electron carrier 1-methoxy-5-methylphenazinium sulfate dimethyl sulfate (1-Methoxy PMS) The dehydrogenase is reduced to a highly water-soluble yellow formazan product (Formazan dye). The amount of formazan produced is directly proportional to the number of living cells. This feature can therefore be used dire...

Embodiment 2VG16

[0052] Example 2 VG161 effectively kills pancreatic cancer cells in vivo

[0053] In vivo pharmacodynamic research is an important process to verify the efficacy of drugs. By constructing a pancreatic cancer subcutaneous tumor model on nude mice and injecting it into the tumor, the therapeutic effect of VG161 in solid tumors is verified.

[0054] Inject BxPC3 cell suspension in the right armpit of nude mice, and tumors will form after 2 weeks, until the size of the tumor reaches 800mm 3 Intratumoral injection of VG161 was performed, and the vehicle was used as a control. Observation indicators include tumor volume change and mouse body weight, which are measured every 3 days, and the survival curve of mice is recorded. Observation endpoints include mouse death or mouse tumor volume exceeding 2000mm 3 .

[0055] In order to explore the optimal concentration of VG161 combined with other drugs, five consecutive and single injections of VG161 at different concentrations were pe...

Embodiment 3

[0059] Example 3 VG161 combined with gemcitabine and nab-paclitaxel

[0060] After obtaining the optimal combination concentration of VG161 based on Example 2, the BxPC3 nude mouse model was established again to explore the therapeutic effect of VG161 combined with the first-line chemotherapy regimen for pancreatic cancer (GEM+Nab-PTX regimen).

[0061] The GEM+Nab-PTX regimen, that is, gemcitabine combined with nab-paclitaxel, is currently the commonly used first-line neoadjuvant chemotherapy regimen for pancreatic cancer. Many studies have confirmed that the combination of the two drugs is beneficial to prolong the survival time of patients with pancreatic cancer. Vehicle was set as the negative control group, and VG161 single drug and GEM+Nab-PTX regimen were set as the positive control group to explore the therapeutic effect of the combined regimen of VG161+GEM+Nab-PTX on pancreatic cancer. At the same time, the administration of VG161 first followed by the GEM+Nab-PTX re...

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Abstract

The invention relates to the technical field of medicines, provides use of an oncolytic virus VG161 in preparation of drugs for treating pancreatic cancer and further provides use of combination of the oncolytic virus VG161, gemcitabine and albumin paclitaxel in preparation of a drug group for treating the pancreatic cancer. Further, the invention further provides a pharmaceutical composition for treating the pancreatic cancer. The pharmaceutical composition is prepared from the oncolytic virus VG161 and a pharmaceutically-acceptable adjuvant. The invention simultaneously provides the drug group for treating the pancreatic cancer. The drug group comprises a forward drug and a subsequent drug, wherein the forward drug is prepared from the oncolytic virus VG161 and a pharmaceutically-acceptable adjuvant, and the subsequent drug is prepared from the gemcitabine and the albumin paclitaxel. Proven by in-vitro cell tests, the single VG161 can be used for effectively killing pancreatic cancer cells; and proven by mouse in-vivo experiments, the single VG161 can be used for effectively treating a transplanted tumor in a mouse model suffering from the pancreatic cancer. By employing combination of the VG161 and a GEM+Nab-PTX scheme, the treatment effect is further improved.

Description

technical field [0001] The invention belongs to the field of biomedicine and relates to the use of oncolytic virus VG161 in the preparation of drugs for treating pancreatic cancer, in particular to the use of it in combination with gemcitabine and nab-paclitaxel in the preparation of drugs for treating pancreatic cancer. Background technique [0002] Up to now, nearly 30 oncolytic virus products have entered various phases of clinical trials worldwide. Among them, H101 (Ankerui), the world's first oncolytic virus drug approved for marketing, was approved by China's State Food and Drug Administration in 2005. It was not until 2015, after 10 years, that an oncolytic virus drug (T-Vec) expressing Granulocyte-macrophage colony stimulating factor (GM-CSF) was launched in the United States, becoming the first Two oncolytic virus products on the market. However, the above products do not carry or only carry one armed gene GM-CSF. Studies in recent years have shown that GM-CSF ca...

Claims

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Application Information

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IPC IPC(8): A61K35/763A61K31/7068A61K31/337A61K47/64A61K47/42A61P35/00
CPCA61K35/763A61K31/7068A61K31/337A61K47/643A61K47/42A61K9/0019A61P35/00A61K2300/00
Inventor 梁廷波白雪莉沈艺南宋巍杨子帆梁兴梅郦宇炜林丹妮
Owner THE FIRST AFFILIATED HOSPITAL ZHEJIANG UNIV COLLEGE OF MEDICINE
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