Oncolytic Adenovirus Therapy for Pancreatic Cancer

Pancreatic cancer is widely known as one of the most lethal forms of cancer. Patients diagnosed with Pancreatic cancer are almost always terminal and have one of the worst 5 year prognoses of all types of cancer. A defining feature of pancreatic cancer is a stroma covering which makes the tumor immunosuppressive. When a tumor begins to form, those tumor cells that carry easily identifiable antigens will be quickly killed off by the host immune system. Over time, the tumor cells that remain will not carry any distinguished antigens thus making the tumor invisible to the host immune system. What results is an effectively impenetrable tumor.

Researchers Callum Nattress and Gunnel Hallden are working with adenoviruses as possible tools to help fight pancreatic cancer. Viruses of the family adenoviridae are small, non-enveloped, double stranded DNA viruses. Importantly, adenovirus infection of cells will eventually cause the host cell to lyse. When a cancerous cell lyses, it releases tumor-associated antigens (TAAs) and damage- and pathogen-associated molecular pattern molecules (DAMPs and PAMPs). These act as the alarm signal to alert the host immune system that something is amiss in that area of the body. Also, just by infecting and destroying some tumor cells, adenoviruses can pave pathways into the tumors which can allow host immune system cells and chemotherapy drugs access to the core of the tumor.

What about non-cancerous cells? While non-cancerous cells can and will be effected by adenovirus, Nattress and Hallden have chosen to work with a very specific serotype of adenovirus - serotype 5 species C (Ad5). They have chosen this specific serotype for many reasons, one of which is that even wild type Ad5 virus causes only mild respiratory tract infections that resolve on their own in immunocompetent individuals. The virus that they will use for treatment will, of course, not be wild type Ad5, but a genetically engineered version of the virus with functions altered to best support cancer destruction. Other reasons are that Ad5 is easy to genetically engineer since it has a relatively small genome and a complete picture of all gene functions has been established.

This is exciting research because we are beginning to realize the potential for oncolytic adenovirus to work synergistically with chemotherapies, activate anti-tumor immune responses, and contribute to tumor stromal dissemination.

Advances in oncolytic adenovirus therapy for pancreatic cancer, Center for Molecular Oncology Barts Cancer Institute. 2018. C. Nattress, G. Hallden. 

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