Cancer Therapy using Engineered Tanapox Virus
Product: Cancer Therapy using Engineered Tanapox Virus
Development Stage: Preclinical In Vivo Proof of Concept
Primary Inventor: Karim Essani, PhD, Biological Sciences
Scientific Publication: Conrad et al. Oncolytic tanapoxvirus expressing FliC causes regression of human colorectal cancer xenografts in nude mice. J Exp Clin Cancer Res. 2015;34(1); Suryawanashi et al. T-independent response mediated by oncolytic tanapoxvirus recombinants expressing interleukin-2 and monocyte chemoattractant protein-1 suppresses human triple negative breast tumors. Med Oncol. 2017;34(6); Zhang et al. Oncolytic Tanapoxvirus Expressing Interleukin-2 is Capable of Inducing the Regression of Human Melanoma Tumors in the Absence of T Cells. Curr Cancer Drug Targets. 2017;17:1-15; Zhang et al. Tanapoxvirus lacking a neuregulin-like gene regresses human melanoma tumors in nude mice. Virus Genes. 2017;53: 52-62; Zhang T and Essani K. Tanapoxvirus lacking the 15L gene inhibits melanoma growth by inducing interferon-位1 release. Virus Genes. 2017;53: 477-482.
License Status: License Available
Patent Status: South Korea 10-1949849-0000; Australia 2015289512, Publication #: US 20107/0165378
Patent Pending: US, Canada, China, EU, India, Japan
Reference: 2014-015
In the US alone, approximately 1.8 million people are expected to be diagnosed with cancer in 2019, and about 600,000 deaths are expected as a result of cancer. Most people will be treated with a combination of radiation, chemotherapy, and/or surgery. However, these standard therapies are associated with severe side-effects including cognitive impairment and organ damage, and in the case of radiation, the potential to cause cancer while attempting to treat it. For these reasons, new therapeutic options are desperately needed.
Recently, new approaches have emerged. One is immunotherapy that activates the immune system against cancer. This approach includes; CAR-T cell therapy, antibody based therapies (anti-CTLA-4/anti-PD-1) and oncolytic viruses (OVs). OVs directly replicate in and destroy cancer cells by; specific infection of cancer cells and activating the patient鈥檚 immune system against the cancer, while not causing viral disease in the patient鈥檚 healthy tissues. OVs are genetically engineered to preferably infect cancer cells, to only replicate in cancer cells, to enhance the patient鈥檚 immune system and to limit viral disease/side-effects.
At WMU, Tanapoxvirus (TPV) has been engineered to not only serve as an anti-cancer agent, but to combine both immunotherapy and virotherapy together for the most efficacious attack on tumor cells. TPV is an attractive candidate for use as an OV because: it causes a mild, self-limiting, febrile illness, it has never been reported to transmit from person to person, and it鈥檚 infection zone has been limited to equatorial Africa, creating a patient population in the rest of the world that is immunologically na茂ve to the virus. Additionally, TPV has a large dsDNA genome allowing extensive modification, and replicates far more slowly when compared to other OVs, delaying the patient鈥檚 anti-viral immune response and facilitating anti-cancer activities by TPV.
Technology Description
Recombinant TPVs have been created that include: a deletion of the viral thymidine kinase gene. allowing for preferential replication of the TPV in cancerous cells, and deletion of the viral 2L gene that neutralizes human tumor necrosis factor (TNF) enhancing the host inflammatory response against the viral-infected cancer cells.
Immuno-stimulatory genes have also been inserted into TPV to activate the patient鈥檚 immune system to attack cancers. TPVs containing: CCL2 (monocyte chemoattractant protein-2), IL-2 (interleukin-2, T-cell growth factor), or a Salmonella typhimurium flagellar protein (FliC) have shown significant reduction of human melanoma, triple negative breast cancer, or colorectal cancer, respectively, in xenografts in nude mice.
Potential Benefits:
- TPV has shown significant reduction of multiple human cancers in nude mice, including: melanoma, triple negative breast cancer, and colorectal cancer
- TPV is an ideal viral therapeutic because it causes mild disease, the patient population is na茂ve to the virus, and it is not transmitted between individuals
- TPV can support extensive genetic modification for creation of multiple anti-cancer therapeutics.