Last month the Journal of Clnical Oncology published some very exciting news. T-Vec, a virus-based therapy, proved to be effective in some melanoma (skin cancer) patients. It is the first time a virus-based therapy has been successful in a big clinical trial. The concept of virus-based therapy is an amazing one, as viruses are parasites that cause some severe and even fatal diseases. Remarkably however, scientists have managed to turn them to our favour in the fight against cancer. While T-Vec therapy is at a very early stage, it is very encouraging to see that the people that did respond to the virus (only 16% of subjects), responded amazingly well, with over 50% alive and still benefiting from the treatment at the end of the study.
The virus used in this study is a modified version of the Herpes Virus A, which normally causes bad cold sores. In order to understand the paradox of how we can benefit from it, it is important to know that viruses are very simple structures. They basically consist of some genetic material wrapped in a membrane or a protein cover. They lack all the machinery necessary to proliferate, so they need to parasitise our cells to reproduce. There are millions of types of viruses which have evolved to infect specific types of cells in our bodies. However, they all have some similarities: in order to survive, they all must enter (infect) the cells of the host, avoid being “seen” by its defences, multiply inside them, and frequently burst the cell in order to free the new viruses so they can in turn infect new cells. And, after millions of years of evolution, they have become very efficient at it.
In the last couple of decades, scientists have been trying to take advantage of the ability of viruses to kill their target cells. By reprogramming their relatively simple genetic code, the aim has been to generate viruses which kill tumour cells while sparing normal cells. The difficult question is how to make the virus tumour-specific. In this case, scientists came up with a clever solution: they exploit the fact that tumour cells “hide” from the immune system to avoid being attacked. And because tumour cells are “invisible”, they also cannot “call” the defences of our immune system when they are in trouble (for example, when it is suffering a viral infection!). Using this fact, the scientists reprogrammed the Herpes Virus A to make it very visible to the immune system. If the viruses now attack healthy cells, these will be able to call the immune system into action and protect themselves. In contrast, when tumour cells get infected, they cannot do this, so the viruses multiply and kill them.
There are of course caveats. The control group in this study wasn’t perfect, so it is difficult to assess the real advantage in survival versus current therapy. Moreover, some patients had to drop the treatment because of the side effects (fever, chills and fatigue, mainly). And most importantly, only 16% of patients responded to the therapy. It is essential that we understand why some responded so well and other didn’t at all in order to predict which patients would benefit from the therapy. Finally, it is worth mentioning that in this clinical trial the viruses were injected directly in the tumour, which is not possible in most kinds of cancers. It remains to be seen if the therapy is still safe and efficient when given through other administration routes.
In spite of all this, the results are undeniably promising and exciting. It will be interesting to see how T-Vec works in combination with other treatments, and in general how much medicine will be able to benefit from the still young field of virus-based therapies.