A modified oncolytic vaccinia virus helps kill pancreatic tumor cells and makes them more vulnerable to immunotherapy in an animal model, shows research from Queen Mary University of London and Zhengzhou University in China.
New treatments are desperately needed for pancreatic cancer. It is relatively common, but has a poor prognosis and is the fourth leading cause of cancer death with a 5-year survival rate of 9% or less.
Oncolytic viruses that are designed to attack tumor cells are a promising therapeutic option for pancreatic cancer, but reliable delivery to the tumor cells has been problematic in the past. This is particularly true for inaccessible or metastatic cancers, where treatment cannot always be injected directly into the tumor.
Yaohe Wang, M.D., Ph.D., a professor at the Barts Cancer Centre at Queen Mary, and his team engineered an oncolytic vaccinia virus to spread more easily between cancer cells in a tumor and between different tumors. They also ‘armed’ the virus with interleukin-21 which can help activate immune T cells to target the cancer.
Vaccinia virus is related to the virus that causes cowpox, used to make the original Jenner smallpox vaccine. A modified vaccinia virus is a good candidate for targeting pancreatic cancer for a number of reasons, according to Wang and team. For example, it does not require a specific surface receptor, it can replicate in low oxygen environments found in treatment-resistant tumor tissue and it can trigger cell death and vascular collapse in the tumor microenvironment.
The researchers tested the efficacy of the modified virus in a mouse and Syrian hamster model of pancreatic cancer. Writing about the research in the Journal for ImmunoTherapy of Cancer, the scientists report that treatment with the virus changed the tumor microenvironment to trigger an antitumor response from the animal’s immune systems.
They also found that the addition of interleukin-21 seemed to make the tumors more susceptible to treatment with a type of immunotherapy drug known as immune checkpoint inhibitor (α-programmed cell death protein 1).
“This platform provides a powerful therapeutic to target multiple aspects of pancreatic cancer simultaneously through a convenient administration approach… significantly improving the prospects of disease eradication and prevention of recurrence in pancreatic cancer patients,” says Wang. “This platform is also suitable for treatment of other human tumor types.”
Treatment of the animals with a combination of the oncolytic virus, the checkpoint inhibitor and a drug (PI3Kδ inhibitor) that stops white blood cells in the immune system from destroying the therapeutic virus led to significantly extended survival in the animal models.
The team has received additional funding from the Medical Research Council in the UK and now hopes to progress the research to phase I clinical trials to assess the efficacy of this treatment in pancreatic cancer patients.
“The current prognosis for patients with pancreatic cancer has not improved for many decades and so we urgently require new treatments that can improve long-term survival,” says Louisa Dunmall, Ph.D., senior postdoctoral researcher at Barts Cancer Institute, Queen Mary University of London and joint first author of the study. “Our platform provides an exciting new mechanism of attacking the tumor in these patients.”