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Combining herpes with chemo can help fight cancer


Hamilton, ON Combining a herpes virus with chemotherapy is showing promise in killing cancer cells and tumours in mice, two McMaster University studies have found.

Led by Sam Workenhe, a postdoctoral researcher in the lab of Karen Mossman, chair of the Department of Biochemistry and Biomedical Sciences and member of the Michael G. DeGroote Institute for Infectious Disease Research and McMaster Immunology Research Center, the research was recently published in the scientific journals Molecular Therapy and Cancer Immunology Research.

“Cancer cells are constantly evolving to outsmart the body’s immune response,” Workenhe says. “Effective cancer therapies target tumour cells directly and initiate an “anti-tumour” immune response that targets tumour cells, even in the absence of the original therapeutic agent.”

The approach is a novel way to directly target tumour cells and activate the immune system, he says.

The researchers study oncolytic viruses, which are novel cancer therapeutics that kill cancer cells but spare normal, healthy cells, “thus mediating their cancer-killing activity without the adverse side effects common with radiation therapy and chemotherapy,” Mossman explains. “In addition to directly killing tumour cells,” she says, “oncolytic viruses activate the host immune response, leading to both clearance of the virus and recognition and clearance of the tumour.”

Workenhe genetically engineered Herpes simplex viruses (HSVs) in a way that makes them specifically replicate in and kill cancer cells. “In our first study we used HSV-1 and HSV-2 oncolytic viruses to activate the immune response, and in a parallel study we combined this with chemotherapy and noticed it induced tumour regression and survival of mice with breast cancer.”

Their work supports recent studies that have found that some kinds of cell death are more beneficial in a therapeutic context compared to other types of cell deaths, he adds. Apoptosis, or programmed cell death, is a ‘quiet’ form of cell death that has evolved not to stimulate an immune response, as it plays an essential role in normal growth and development. Most viruses induce apoptosis following infection. However, Workenhe found that HSV vectors that preferentially induce a different type of cell death, called ‘immunogenic cell death’, are better stimulators of the immune response, and better oncolytic vectors. Synergistic effects on tumour regression and subsequent survival were observed when the virus was used in combination with an approved chemotherapy drug also known to induce immunogenic cell death.

The team plans to expand their work, which currently focuses on breast cancer, to other types of cancer, using a variety of combination therapy strategies.

The study also involved work by IIDR member Brian Lichty, associate professor of pathology and molecular medicine, and his postdoctoral researcher Jonathan G. Pol.

The study was supported by operating grants from the Canadian Cancer Society, the Canadian Breast Cancer Research Alliance and the Cancer Research Society.

 

Reported by Chantall Van Raay, McMaster University