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Cancer Therapy using Engineered Tanapox Virus



Product: Cancer Therapy using Engineered Tanapox Virus

Development Stage: Preclinical In Vivo Proof of Concept

Primary Inventors: Karim Essani, PhD, Biological Sciences

Scientific Publication: Conrad et al., J Exp & Clin Cancer Res (2015) 34:19

License Status: License Available

Patent Status: US Provisional Application Filed: 62/025,734; PCT Applications: Australia, Canada, China, EU, India, Indonesia, Japan, Phillippines, South Africa, and South Korea

Reference: 2014-015

Contact: Clark Bennett PhD
dclark.bennett@wmich.edu

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     Globally, colorectal cancer in humans (hCRC) is the second-most common cancer in women and the third-most common in men. In the United States, the five-year survival rate for patients with all stages of hCRC improved by 14% between 1977 and 2006, from 51% to 65%. However, established therapies are often inadequate for patients with advanced disease. For patients with advanced stage hCRC (stage III or IV), the five-year survival rate is less than 20%. New treatments and treatment modalities are desperately needed.
     Recognition that the body’s immune system can be mobilized to help fight cancer has recently led to multiple therapeutic modalities that activate the body’s innate and/or adaptive immune system. One new modality is oncolytic viruses that are engineered to assist the host immune system to recognize and attack cancer cells.
     Specifically, tanapox virus (TPV) is an attractive candidate for oncolytic virotherapy. TPV infected humans experience only a mild and self-limiting febrile illness, in part because TPV infection is normally confined to peripheral areas of the body. Additionally, TPV has never been observed to transmit from person to person, a highly desirable safety feature in an oncolytic virus.

Technology Description
     At WMU, recombinant TPV have been created that have the viral thymidine kinase (TK) gene deleted (Δ66R), in order to specifically replicate in cancer cells that characteristically over-produce TK. Other recombinant TPV have been created that have their 2L gene deleted (Δ2L). The TPV 2L protein binds and neutralizes cellular TNF decreasing the host inflammatory and antiviral immune responses. One TPV double mutant (Δ2L, Δ66R) was also engineered to express fliC to specifically tag the cancer cells with an immunogenic marker. The fliC protein is a highly immunogenic bacterial flagellin protein that is an activator of the host’s innate immune response. The recombinant TPV/Δ2L66R /fliC has demonstrated impressive oncolytic activity through regression of hCRC xenografted tumors in athymic nude mice.

Potential Benefits
  • TPV/Δ2L/Δ66R/fliC regresses hCRC tumors in mice with innate immunity
  •  TPV/Δ2L/Δ66R/fliC specifically replicates in cancer cells, stimulates host innate immunity, and does not reduce host TNF inflammatory responses
  •  Wild-type TPV causes very mild illness and is not transmitted from person to person making it desirable for cancer therapy   

Cancer Therapy using Engineered Tanapox Virus


     Globally, colorectal cancer in humans (hCRC) is the second-most common cancer in women and the third-most common in men. In the United States, the five-year survival rate for patients with all stages of hCRC improved by 14% between 1977 and 2006, from 51% to 65%. However, established therapies are often inadequate for patients with advanced disease. For patients with advanced stage hCRC (stage III or IV), the five-year survival rate is less than 20%. New treatments and treatment modalities are desperately needed.
     Recognition that the body’s immune system can be mobilized to help fight cancer has recently led to multiple therapeutic modalities that activate the body’s innate and/or adaptive immune system. One new modality is oncolytic viruses that are engineered to assist the host immune system to recognize and attack cancer cells.
     Specifically, tanapox virus (TPV) is an attractive candidate for oncolytic virotherapy. TPV infected humans experience only a mild and self-limiting febrile illness, in part because TPV infection is normally confined to peripheral areas of the body. Additionally, TPV has never been observed to transmit from person to person, a highly desirable safety feature in an oncolytic virus.

Technology Description
     At WMU, recombinant TPV have been created that have the viral thymidine kinase (TK) gene deleted (Δ66R), in order to specifically replicate in cancer cells that characteristically over-produce TK. Other recombinant TPV have been created that have their 2L gene deleted (Δ2L). The TPV 2L protein binds and neutralizes cellular TNF decreasing the host inflammatory and antiviral immune responses. One TPV double mutant (Δ2L, Δ66R) was also engineered to express fliC to specifically tag the cancer cells with an immunogenic marker. The fliC protein is a highly immunogenic bacterial flagellin protein that is an activator of the host’s innate immune response. The recombinant TPV/Δ2L66R /fliC has demonstrated impressive oncolytic activity through regression of hCRC xenografted tumors in athymic nude mice.

Potential Benefits
  • TPV/Δ2L/Δ66R/fliC regresses hCRC tumors in mice with innate immunity
  •  TPV/Δ2L/Δ66R/fliC specifically replicates in cancer cells, stimulates host innate immunity, and does not reduce host TNF inflammatory responses
  •  Wild-type TPV causes very mild illness and is not transmitted from person to person making it desirable for cancer therapy   

Product: Cancer Therapy using Engineered Tanapox Virus

Development Stage: Preclinical In Vivo Proof of Concept

Primary Inventors: Karim Essani, PhD, Biological Sciences

Scientific Publication: Conrad et al., J Exp & Clin Cancer Res (2015) 34:19

License Status: License Available

Patent Status: US Provisional Application Filed: 62/025,734; PCT Applications: Australia, Canada, China, EU, India, Indonesia, Japan, Phillippines, South Africa, and South Korea

Reference: 2014-015

Contact: Clark Bennett PhD
dclark.bennett@wmich.edu

Download PDF