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Pharmaceutical composition for treating cancer comprising anti-cancer virus, immune checkpoint inhibitor and hydroxyurea as active ingredients

A technology of immune checkpoints and active ingredients, applied in the field of pharmaceutical compositions for the treatment of cancer, can solve problems such as persistent response or complete response, progressive disease, acute tumor necrosis, etc., and achieve excellent anti-cancer effects and safety effects

Pending Publication Date: 2022-04-15
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

[0004] In multiple clinical studies of vaccinia virus-based oncolytic viruses, oncolytic virus therapy may result in acute tumor necrosis, durable responses, or complete responses, but in some cases, may lead to unpredictable outcomes (pharmacodynamic variability ), such as progressive disease or premature death

Method used

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  • Pharmaceutical composition for treating cancer comprising anti-cancer virus, immune checkpoint inhibitor and hydroxyurea as active ingredients
  • Pharmaceutical composition for treating cancer comprising anti-cancer virus, immune checkpoint inhibitor and hydroxyurea as active ingredients
  • Pharmaceutical composition for treating cancer comprising anti-cancer virus, immune checkpoint inhibitor and hydroxyurea as active ingredients

Examples

Experimental program
Comparison scheme
Effect test

preparation Embodiment 1

[0106] Preparation Example 1. Production of oncolytic virus (Wyeth VV tk- 、WR VV tk- )

preparation Embodiment 11

[0107] Preparation Example 1.1. Construction of Shuttle Plasmid Vector

[0108] To produce oncolytic viruses lacking the thymidine kinase (TK) gene, wild-type vaccinia viruses, ie, Wyeth strain (NYC Health Department) and Western Reserve strain, were purchased from American Type Culture Collection (ATCC). For recombination, the TK region in wild-type vaccinia virus was replaced with a shuttle plasmid vector containing the firefly luciferase reporter (p7.5 promoter) gene or the GFP gene.

preparation Embodiment 12

[0109] Preparation Example 1.2. Production of Oncolytic Viruses

[0110] To obtain oncolytic virus, HeLa cells (ATCC) were grown at 4 × 10 5 Cells were seeded in 6-well plates and cultured in EMEM medium containing 10% fetal bovine serum. Subsequently, wild-type vaccinia virus was treated at an MOI of 0.05. After 2 hours, the medium was replaced with EMEM medium containing 2% fetal bovine serum, and then cells were transfected with 4 μg of the shuttle plasmid vector constructed in Example 1.1, and Xfect TM The polymer (Clonetech 631317, USA) was linearized. Incubation was carried out for 4 hours. Subsequently, the medium was replaced with EMEM medium containing 2% fetal bovine serum, and then culture was performed for 72 hours. Finally, the infected cells were collected, and then the freeze-thaw was repeated 3 times. Subsequently, the cells were lysed by ultrasound, and the free oncolytic virus was obtained by the sucrose cushion method, named Wyeth VV tk- or WRVV tk- ....

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Abstract

The present invention relates to a pharmaceutical composition for treating cancer, comprising an anti-cancer virus, an immune checkpoint inhibitor, and hydroxyurea as active ingredients. The pharmaceutical composition for treating cancer according to the present invention comprises an anti-cancer virus, an immune checkpoint inhibitor, and hydroxyurea as active ingredients, and has excellent anti-cancer effect and safety compared to conventional cases in which the anti-cancer virus is administered alone or in combination with the anti-cancer virus and the immune checkpoint inhibitor. Therefore, the pharmaceutical composition for treating cancer of the present invention, comprising an anti-cancer virus, an immune checkpoint inhibitor, and hydroxyurea as active ingredients, can be effectively used for treating cancer.

Description

technical field [0001] The present invention relates to a pharmaceutical composition for treating cancer, the pharmaceutical composition comprising an oncolytic virus, an immune checkpoint inhibitor and hydroxyurea as active ingredients. Background technique [0002] Oncolytic viruses have excellent tumor-specific targeting ability, proliferation ability in cancer cells and cancer cell killing ability. Recently, various clinical studies based on oncolytic viruses have been conducted. In 2015, the U.S. and Europe ushered in the field of oncolytic viruses with the successful commercialization of herpes simplex virus-based oncolytic virus talimogene laherparepvec (T-Vec) as a treatment for advanced melanoma. [0003] Recently, the utility of oncolytic viruses exceeded their own efficacy, and viruses activated tumor immunity, thereby showing their potential as therapeutic agents in combination with another immunotherapeutic agent. Until 2000, which was the early stage of oncol...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K35/76A61K39/395A61K31/155A61P35/00A61K39/00
CPCA61K39/395A61P35/00Y02A50/30A61K35/768C12N2710/24121C12N2710/24143C12N2710/24132C12N7/00C12N15/86C07K16/2818C07K16/2827A61K45/06A61K31/17A61K2300/00A61K35/76A61K39/3955C12N2710/24021C12N2710/24162
Inventor 黄泰皓赵檬
Owner 拜耳诺克斯有限公司
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