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Oncolytic rhabdovirus expressing il12

A virus and oncolytic technology, applied in the field of recombinant oncolytic rhabdovirus, can solve the problem of reducing effectiveness

Pending Publication Date: 2019-07-23
TURNSTONE LLP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0007] Cytokines, such as IL-12, have also been used to direct antitumor immune responses, but the short half-lives of these cytokines when administered as proteins, and the dose-limiting toxicities encountered after systemic administration, have reduced their potential effectiveness (5)

Method used

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  • Oncolytic rhabdovirus expressing il12
  • Oncolytic rhabdovirus expressing il12
  • Oncolytic rhabdovirus expressing il12

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Embodiment Construction

[0101] MG1-IL12 ICV enhances NK cell-mediated tumor rejection.

[0102] The authors of the present disclosure have previously demonstrated that ex vivo infection of autologous tumor cells with an oncolytic virus can elicit a robust immune response against established, non-permissive tumors in vivo (15). To determine whether MG1 and MG1-IL12 could similarly induce immune responses when used as ICV, the authors injected intravenously (i.v.) 5x10 5 Ɣ-irradiated B16F10 cells that were either mock-infected or infected with MG1 or MG1-IL12. The authors have previously demonstrated that intravenous administration of ICV is associated with rapid and dose-dependent accumulation of injected cells in the lung lasting up to 1 day in tumor-free animals (16). After ICV delivery, significantly higher levels of IL12 were detected in lung homogenates of mice receiving MGI-IL12 ICV compared with animals receiving ICV of cells alone or MG1 ( Figure 6 , t = 24 hours). To determine whether in...

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Abstract

Disclosed herein is an oncolytic recombinant Maraba virus whose genome comprises one or more nucleic acid sequences that, in combination, encode an interleukin-12 (IL12) protein or a functional portion thereof. A method for treating a cancer in a patient using the oncolytic recombinant Maraba virus is also disclosed. The present disclosure also provides a tumour cell infected with an oncolytic rhabdovirus whose genome comprises one or more nucleic acid sequences that, in combination, encode an interleukin-12 (IL12) protein or a functional portion thereof, for use as an infected cell vaccine (ICV) for the treatment of a cancer. A method for treating a cancer in a patient using the infected cell vaccine is also disclosed.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of priority to U.S. Provisional Patent Application No. 62 / 372,406, filed August 09, 2016, the entire contents of which are incorporated herein by reference. technical field [0003] The present disclosure relates to recombinant oncolytic rhabdoviruses expressing interleukin-12. Background technique [0004] The following paragraphs are not an admission that anything discussed therein is prior art or part of the knowledge of those skilled in the art. [0005] Oncolytic viruses (OVs) are promising anticancer therapeutics that are designed or selected to infect and multiply in tumor cells while possessing attenuated replication capacity in normal tissues. One characteristic important to the potency of some OVs is the ability to stimulate an anti-tumor immune response. [0006] Vaccination of the patient's own cancer cells (autologous cell vaccines) has been attempted in the past with ...

Claims

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Application Information

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IPC IPC(8): C12N7/01A61K35/766A61K38/20A61P35/00C07K14/145C07K14/54C12N15/24C12N15/47C12N15/86C12N5/10
CPCC12N5/10A61P35/00A61K38/208A61K35/768C12N2760/20232C12N2760/20243A61K35/766A61K38/20C07K14/54A61K9/0019C07K14/145C07K14/5434C12N15/86C12N2760/20041
Inventor 阿尔莫哈纳德·阿尔卡亚尔丽贝卡·奥尔约翰·卡梅伦·贝尔
Owner TURNSTONE LLP
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