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Novel recombinant oncolytic vaccinia virus for blocking immune inspection point and activating immune co-stimulation, construction method for novel recombinant oncolytic vaccinia virus and application of Novel recombinant oncolytic vaccinia virus

An immune checkpoint, vaccinia virus technology, applied in the field of tumor biology, can solve the problem of lack of recombinant oncolytic vaccinia virus, and achieve the effect of significant anti-tumor effect, prolong survival period, and activate anti-tumor immune response

Pending Publication Date: 2020-12-18
NANJING VIROTHER BIOPHARMACEUTICAL CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Currently, there is a lack of a recombinant oncolytic vaccinia virus capable of both blocking immune checkpoints and activating immune co-stimulatory pathways

Method used

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  • Novel recombinant oncolytic vaccinia virus for blocking immune inspection point and activating immune co-stimulation, construction method for novel recombinant oncolytic vaccinia virus and application of Novel recombinant oncolytic vaccinia virus
  • Novel recombinant oncolytic vaccinia virus for blocking immune inspection point and activating immune co-stimulation, construction method for novel recombinant oncolytic vaccinia virus and application of Novel recombinant oncolytic vaccinia virus
  • Novel recombinant oncolytic vaccinia virus for blocking immune inspection point and activating immune co-stimulation, construction method for novel recombinant oncolytic vaccinia virus and application of Novel recombinant oncolytic vaccinia virus

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Embodiment 1

[0035] A novel recombinant oncolytic vaccinia virus of the present invention that blocks immune checkpoints and activates immune co-stimulatory signaling pathways, the thymidine kinase TK region of the recombinant oncolytic vaccinia virus genome contains the extracellular domain gene of CD155 protein, and Able to express soluble protein sCD155.

[0036] The amino acid sequence of the soluble protein sCD155 is shown in SEQ ID NO:1.

[0037] The recombinant oncolytic vaccinia virus is capable of oncolysis.

[0038] The method for constructing a novel recombinant oncolytic vaccinia virus VV-sCD155 that blocks immune checkpoints and activates immune co-stimulatory pathways of the present invention comprises the following steps:

[0039] (1) artificially synthesizing the sCD155 gene fragment, the nucleotide sequence of the gene fragment is shown in SEQ ID NO.2;

[0040] (2) Subcloning the sCD155 gene fragment into the vaccinia virus shuttle plasmid pVV-EGFP by restriction enzyme ...

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Abstract

The invention discloses a novel recombinant oncolytic vaccinia virus for blocking immune inspection point and activating immune co-stimulation signal channels, a construction method for the novel recombinant oncolytic vaccinia virus and application of the novel recombinant oncolytic vaccinia virus. The novel recombinant oncolytic vaccinia virus for blocking the immune inspection point and activating the immune co-stimulation signal channels can selectively replicate in tumor cells and dissolve the tumor cells and meanwhile express and secrete a soluble protein sCD155; and the soluble protein sCD155 is an extracellular region of a protein CD155 and can specifically bond acceptors TIGIT and CD226 of the protein CD155. The novel recombinant oncolytic vaccinia virus VV-sCD155 disclosed by theinvention has multiple antitumor actions of dissolving tumors, activating antitumor immunization and the like, only selectively replicates in the tumor cells, has very high safety and has a good antitumor drug development prospect.

Description

technical field [0001] The invention relates to the field of tumor biotechnology, in particular to a novel recombinant oncolytic vaccinia virus that blocks immune checkpoints and activates immune co-stimulatory signaling pathways, and its construction method and application. Background technique [0002] Cancer is one of the most harmful diseases to human life and health, and millions of people die of cancer every year. Many patients are already in the middle and late stage at the time of diagnosis and thus lose the chance of surgical treatment. Traditional radiotherapy and chemotherapy have not made breakthroughs, and even small-molecule targeted drugs are still facing the huge challenge of short-term recurrence. [0003] In the past ten years, exciting results have emerged in the clinical research of anti-tumor immunotherapy, bringing hope to cancer patients again. As early as 1090, German scientist (Nobel Prize winner) Paul Ehrlich proposed that the immune system has th...

Claims

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Application Information

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IPC IPC(8): C12N7/01C12N15/863A61K35/768A61K38/17A61K48/00A61P35/00C12R1/93
CPCC07K14/70596C12N15/86A61K35/768A61K48/0025A61K48/005A61K38/177A61P35/00C12N2710/24021C12N2710/24043C12N2710/24032A61K2039/5256
Inventor 魏继武左曙光魏敏王士群董杰陈安仙
Owner NANJING VIROTHER BIOPHARMACEUTICAL CO LTD
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