One Plus One Equals Three in Gene Therapy for Cancer Study

A new approach to treating cancer is the use of engineered viruses that infect and kill tumours without damaging normal tissues. These so-called oncolytic, or cancer-destroying, viruses behave like tiny biological battleships, capable of directly and specifically attacking cancer cells. Immunotherapy is another promising anti-cancer strategy that seeks to educate a cancer patient’s own immune system to recognize tumor cells as foreign bodies and destroy them.

Researchers at McMaster University in Canada have found a way to combine these two exciting therapeutic approaches so that they are even more effective in their attack on cancer. In other words, by adjusting the timing and method of combining viral and immune therapy they have made "one plus one equal three!"

To carry out these studies, the scientists designed a very aggressive cancer model in mice. A rapidly growing, deadly melanoma or skin tumor was injected into the brains of normal animals. By implanting the tumor into the brain, researchers were mimicking a common problem in human patients wherein tumors from other areas of the body nest in the brain – often ultimately leading to death.

The scientists used a "vaccination strategy" to attempt to treat the cancer in the brain by stimulating the mouse’s immune system to recognize the tumor as foreign and were able to modestly extend the survival of the mice. In other mice they then tried to use an oncolytic virus to directly infect and kill the tumors; although they saw some rapid tumor shrinkage, the cancer grew back and there was no impact on mouse survival.

Then researchers combined their vaccination strategy with the oncolytic virus approach but added a twist. They reconstructed the oncolytic virus so that it had both direct cancer-killing and vaccination properties. They used the vaccine to prime, or prepare, the mouse’s immune system, then boosted the immune system with the oncolytic virus treatment. The results were unprecedented – about 20% of the animals appeared to be cured of their disease! These promising animal studies lay the ground work for testing this innovative strategy in human cancer patients.