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Oncolytic virus with improved safety and anticancer effects

An oncolytic virus, vaccinia virus technology, applied in the direction of anti-tumor drugs, resistance to vector-borne diseases, viruses, etc., can solve the controversial problem of additional cytotoxic effect, and achieve the effect of enhancing anti-tumor effect

Pending Publication Date: 2022-02-25
拜耳诺克斯有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the additional cytotoxic effect of coadministration of GCV remains controversial

Method used

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  • Oncolytic virus with improved safety and anticancer effects
  • Oncolytic virus with improved safety and anticancer effects
  • Oncolytic virus with improved safety and anticancer effects

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0118] The preparation of the vaccinia virus of embodiment 1 mutation

Embodiment 11

[0119] Example 1.1 Construction of Shuttle Plasmid Vector

[0120] The shuttle plasmid vector used was a shuttle generated by synthesizing the type 1 HSVTK gene (pSE / L promoter) and firefly luciferase reporter (p7.5 promoter) gene and recombining these genes into the pUC57amp+ plasmid (Genewiz, USA) Plasmid vector.

Embodiment 12

[0121] Construction of the vaccinia virus (C1, C3, C40, C45, C52, and C57) of the mutation of embodiment 1.2

[0122] figure 1 The steps for making the mutant vaccinia virus are shown. Specifically, first, in order to obtain the recombinant virus, HeLa cells (ATCC) were cultured at 4×10 per well 5 The cells were seeded in 6-well plates, and then supplemented with EMEM medium containing 10% fetal bovine serum. The Wyeth wild-type vaccinia virus (New York City Department of Health strain, WR-1536, ATCC) was used for treatment at an MOI of 0.05. After 2 hours, replace the medium with EMEM medium containing 2% fetal bovine serum and use Xfect TM Polymer (Clonetech631317, USA) delivered 4 μg of the shuttle plasmid vector (constructed as in Example 1.1) into the cells. After culturing for 4 hours, the culture medium was replaced with EMEM medium containing 2% fetal calf serum, and culture was continued for 72 hours. The recombinant vaccinia virus containing HSV1-TK gene was obt...

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Abstract

The present invention relates to an oncolytic virus with improved safety and anticancer effects, and a use thereof. The oncolytic virus with improved safety and anticancer effects according to the present invention can express an HSV-TK fragment which contains an effector domain composed of a minimum amino acid sequence capable of phosphorylating GCV or ACV while having no thymidine kinase (TK) activity, or a variant thereof to phosphorylate GCV or ACV, thereby killing cancer cells infected with the oncolytic virus and even neighboring cancer cells. In addition, GCV or ACV is involved in the suppression of viral proliferation and thus, can regulate virus-induced side effects even upon the administration of a high dose of the virus. Furthermore, an anticancer effect is increased even though the number of viral particles is reduced due to suppression of GCV against viral proliferation. Therefore, the oncolytic virus with improved safety and anticancer effects according to the present invention can be advantageously used for treating cancer.

Description

technical field [0001] The invention designs an oncolytic virus with improved safety and anti-tumor effect and its application. Background technique [0002] With the comprehensive use of gene recombination technology, clinical research has begun to use oncolytic viruses with enhanced tumor selectivity and anti-tumor effects. The first recombinant oncolytic virus reported in the literature was a herpes simplex virus. Since then, research on oncolysis using other viruses has also been actively pursued. [0003] The use of oncolytic viruses has attracted increasing attention as the herpesvirus-based T-Vec (Talimogene laherparepvec) has been successfully commercialized in the United States and Europe for the treatment of advanced melanoma. On the other hand, thymidine kinase (TK) gene-deficient vaccinia virus also has a large number of clinical applications; however, due to its narrow therapeutic window, it is limited in maximizing the clinical effect of the virus. For thymi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N7/01C12N15/54A61K35/768A61K31/522A61P35/00C12R1/93
CPCC12N7/00C12N9/1211A61K35/768A61K31/522A61P35/00C12Y207/01021C12N2710/24121C12N2710/24132C12N2710/24151A61K2300/00A61K38/45A61K45/06A61K31/17C12N15/86C12N2710/24143C12N2710/16622A61K35/761A61K35/763C12N9/12
Inventor 黄泰皓赵蒙
Owner 拜耳诺克斯有限公司