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A replication-type oncolytic adenovirus that activates immune co-stimulation by immune checkpoints and its construction method and application

An oncolytic adenovirus and immune checkpoint technology, applied in the field of tumor biology, can solve the problem of lack of replicating oncolytic adenovirus, and achieve the effects of inhibiting tumor growth, ensuring safety, and strongly activating anti-tumor immunity.

Active Publication Date: 2022-06-21
NANJING VIROTHER BIOPHARMACEUTICAL CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] Currently, there is a lack of a replicating oncolytic adenovirus capable of simultaneously blocking immune checkpoints and activating immune co-stimulatory pathways

Method used

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  • A replication-type oncolytic adenovirus that activates immune co-stimulation by immune checkpoints and its construction method and application
  • A replication-type oncolytic adenovirus that activates immune co-stimulation by immune checkpoints and its construction method and application
  • A replication-type oncolytic adenovirus that activates immune co-stimulation by immune checkpoints and its construction method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Construction, preparation, evaluation of anti-tumor immune activation and evaluation of anti-tumor effect of a novel replicative oncolytic adenovirus Ad5sPVR

[0039] 1 Experimental materials and methods

[0040] 1. Experimental Materials and Methods

[0041] 1.1 Experimental materials and instruments

[0042] 1.1.1 Experimental cell lines

[0043] Human embryonic kidney cell line 293T; human liver cancer cell line LM3; mouse melanoma cell line B16 / F10; mouse liver cancer cell line H22 and Hepa1-6; mouse breast cancer cell line 4T1. The above cells were all cultured in a high-glucose DMEM medium containing 10% fetal bovine serum, 100 U / I penicillin and 1 mg / ml streptomycin in a 37°C, 5% CO2 incubator.

[0044] 1.1.1.2 Experimental Apparatus

[0045] Biological safety cabinet (III advance, Class II Biological SafetyCabinet, The Baker Company), carbon dioxide incubator (FORMA SERIES II WATER JACKETCO 2 incubator, Thermo), low temperature centrifuge (HERAEUS MEGAFUGE1....

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Abstract

The invention discloses a replicating oncolytic adenovirus that blocks immune checkpoints and activates immune co-stimulatory signaling pathways and its construction method and application. The novel blocking immune checkpoints and activating the replication of immune co-stimulatory signaling pathways Recombinant oncolytic adenovirus, capable of replicating in tumor cells, expressing and secreting soluble protein sPVR; the soluble protein is the extracellular region of the PVR protein specifically binding to TIGIT and CD226, and the sPVR protein has simultaneous Block the immune negative regulation mediated by the immune checkpoint TIGIT, and activate the anti-tumor immune function mediated by the costimulatory pathway CD226. The novel replication-type oncolytic adenovirus AD5sPVR of the present invention has a strong effect of activating anti-tumor immunity, has remarkable anti-tumor activity and safety, and has a very high prospect and value for developing anti-tumor drugs.

Description

technical field [0001] The invention relates to the field of tumor biotechnology, in particular to a replication-type oncolytic adenovirus that blocks immune checkpoints and activates immune costimulation signaling pathways, and a construction method and application thereof. Background technique [0002] Cancer is one of the most harmful diseases to human life and health, and millions of people die from cancer every year. Many patients are already in the middle and late stages at the time of diagnosis and thus lose the opportunity for surgical treatment. Traditional radiotherapy and chemotherapy have not brought breakthrough progress to the tumor. Even small molecule targeted drugs face the huge challenge of short-term recurrence. . [0003] In the past decade, the exciting results of anti-tumor immunotherapy clinical research have brought hope to tumor patients. As early as 1090, German scientist (Nobel Prize winner) Paul Ehrlich proposed that the immune system has the ab...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12N7/00A61K35/761A61K39/00A61P35/00C12R1/93
CPCC12N7/00A61K35/761A61K39/001129A61P35/00C12N2710/10332C12N2710/10321C12N2710/10334C12N2710/10351A61K2039/5256A61K2039/53A61K2300/00Y02A50/30
Inventor 魏继武张海林张永辉吴俊华董杰
Owner NANJING VIROTHER BIOPHARMACEUTICAL CO LTD
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