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Use of myxoma virus for the therapeutic treatment of cancer and chronic viral infection

a technology of myxoma virus and cancer, applied in the field of myxoma virus therapy, can solve the problems of inability unable to achieve effective cancer treatment, and unable to meet the needs of patients with cancer

Inactive Publication Date: 2006-11-23
THE JOHN P ROBARTS RES INST
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

"The present invention provides a method for inhibiting or treating a cell that has a deficient innate anti-viral response using a modified version of the rabbit Myxoma virus. The virus can selectively infect cells that have a deficient innate anti-viral response, including those that are non-responsive to interferon. The virus can also be used to detect and image cells with a deficient innate anti-viral response in vivo. The technical effects of the invention include the development of a new tool for inhibiting or treating cells with a deficient innate anti-viral response, as well as a method for identifying and imaging these cells."

Problems solved by technology

Current treatments used to treat various types of cancer tend to work by poisoning or killing the cancerous cell.
Unfortunately, treatments that are toxic to cancer cells typically tend to be toxic to healthy cells as well.
Moreover, the heterogenous nature of tumours is one of the primary reasons that effective treatments for cancer remain elusive.
These types of therapies are considered blunt tools that have limited applicability due to the varying types of tumour cells and the limited window in which these treatments can be administered.
Since the replication selective oncolytic virus does not replicate efficiently in normal cells, toxicity to the patient should be low, particularly in comparison to traditional therapies such as radiation or chemotherapy.
However, it is unknown which viruses will best fulfill the oncolytic goals of sustained replication, specificity and potent lytic activity.
Clinical work has shown that current oncolytic viruses are indeed safe, but are not potent enough as monotherapies to be completely clinically effective.
However, the application of such a common human pathogen is limited, as it is likely that the general population has been exposed and acquired an immune response to this virus, which would attenuate the lytic effect of the virus.
HSV can also cause serious side effects or a potentially fatal disease.
However, Reovirus is difficult to genetically manipulate and its viral replication cannot be easily shut off.
However, VSV suffers from the same problems as the Reovirus in that it is difficult to genetically manipulate and its viral replication cannot be easily shut off.

Method used

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  • Use of myxoma virus for the therapeutic treatment of cancer and chronic viral infection
  • Use of myxoma virus for the therapeutic treatment of cancer and chronic viral infection
  • Use of myxoma virus for the therapeutic treatment of cancer and chronic viral infection

Examples

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examples

Virus Strains

[0116] Viral strains used include wildtype MV, MV modified to express either green fluorescence protein (“GFP”) or β-galactosidase (“LacZ”), and killed (“dead”) MV. Viruses were prepped and titred using standard techniques.

Cell Strains

[0117] Mouse experiments were performed using mouse embryo fibroblasts (“MEFs”) derived from a wild-type mouse, and from the following mouse knockouts: IFNα / β receptor homozygous knockout; STAT1 homozygous knockout; PKR heterozygous; RNaseL heterozygous knockout; Mx1 heterozygous knockout; triple PKR / RNaseL / Mx1 homozygous knockout.

[0118] Human experiments were performed on BGMK control cells and human tumour cell lines HT29, HOP92, OVCAR4, OVCAR5, SK-MEL3, SK-MEL28, M14, SKOV3, PC3, DUI45, CAKI-1, 786-0, T47D, MDAMB 435, SF04, U87, A172, U373, Daoy and D384 as described in Stojdl et al., Cancer Cell (2003) 4: 263-275.

Methods

[0119] Generally, assays and experiments were performed as described in Lalani et al. Virology (1999) 256: 2...

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Abstract

The present invention relates to therapeutic use of Myxoma virus. Myxomas virus can selectively infect cells that have a deficient innate anti-viral response, including cells that are not responsive to interferon and can be used to treat diseases characterized by the presence of such cells, including cancer.

Description

FIELD OF THE INVENTION [0001] The present invention relates generally to therapeutic use of Myxoma virus. BACKGROUND OF THE MENTION [0002] Current treatments used to treat various types of cancer tend to work by poisoning or killing the cancerous cell. Unfortunately, treatments that are toxic to cancer cells typically tend to be toxic to healthy cells as well. Moreover, the heterogenous nature of tumours is one of the primary reasons that effective treatments for cancer remain elusive. Current mainstream therapies such as chemotherapy and radiotherapy tend to be used within a narrow therapeutic window of toxicity. These types of therapies are considered blunt tools that have limited applicability due to the varying types of tumour cells and the limited window in which these treatments can be administered. [0003] Modern anticancer therapies currently being developed attempt to selectively target tumour cells while being less toxic to healthy cells, thereby being more likely to leave ...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K48/00A61K39/12A61K35/76A61K35/768A61P31/12A61P35/00
CPCA61K35/13C12N2710/24032A61K35/76A61K35/768A61P31/12A61P35/00A61P35/02A61P43/00Y02A50/30C12N7/00
Inventor MCFADDEN, GRANTBELL, JOHN C.
Owner THE JOHN P ROBARTS RES INST
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