I’d written before about a modified form of HIV (the virus that causes AIDS) being used in the treatment of leukemia. Now, a retroviral cousin of HIV is being used to help target brain cancer.
Viruses have been known to cause some types of cancer for a long time. Rous sarcoma virus, discovered over 100 years ago by Peyton Rous, was found to cause sarcomas (malignant cancers of connective tissues like cartilage, muscle, bone, etc.) in chickens.
Though, at the time, little was known about what the organism was. It was at first just referred to as an “infectious agent.” In time, it was demonstrated that this agent was a virus, later found to be a retrovirus. It was the first oncovirus (a virus known to be a cause of some cancers) ever discovered.
Other retroviruses were discovered over time, some could cause tumors and others weren’t able to do so. Investigators continued to work on retroviruses to see how they were made, how they functioned, how they might trigger cancer and how to inhibit them. As technical advances occurred, more and more was learned. And new retroviruses were continuing to be discovered, as well. But research money doesn’t always flow in a steady stream. There was always more work to do with limited funding.
Fast forward to the early 1980s. HIV was isolated in the early 1980s and was found to be a retrovirus. Initially, funds weren’t plentiful for research on HIV. Investigators had to scramble for whatever money they could get. Some used their own funds or took pay cuts to keep working on HIV. But, as money finally became available, more interest was focused on HIV, and, by association, its sister retroviruses.
Now, let’s discuss the retroviral cousin of HIV that is being used to help target brain cancer.
The retrovirus chosen is a modified form of a virus called Toca 511. Toca 511 has been designed to infect only brain tumor cells – it doesn’t infect healthy cells surrounding the tumor. The virus carries a gene that it implants into the tumor’s DNA. That gene encodes for the production of an enzyme. That enzyme causes the conversion of an antifungal drug, flucytosine, to a chemotherapy drug 5-fluorouracil in each tumor cell that is infected by Toca 511. Since only the tumor cells have the necessary enzyme, only the tumor cells produce 5-fluorouracil. The drug then selectively kills the neoplasm and surrounding tissue is relatively unharmed. 5-fluorouracil, when given IV, affects many cell types and can cause some unpleasant side effects. Here, the chemotherapy is highly localized and doesn’t produce systemic effects. And the flucytosine is given orally so no need for IV access.
But how to get the Toca 511 to the brain tumor? How to make sure that all of the tumor cells get infected, get the gene, develop the enzyme and commit suicide when exposed to the flucytosine?
Inject it. But not by IV, that wouldn’t guarantee that all of the tumor cells got the maximal viral dose. inject it directly into the brain tumor. To do that, neurosurgeons use stereotactic surgery (think The Terminal Man, by Michael Crichton).
The patient’s head is placed in a frame that prevents motion. The brain and tumor are imaged to get a precise 3D location. A small area of bone is removed from the skull and a needle is introduced through the brain into the tumor. Precise location is established by imaging. A syringe containing a solution of Toca 511 is attached and the infusion begins. The surgeons can move the needle to make sure that as many areas of the tumor as possible get injected. After the virus in injected, the needle is removed, skull hole closed and patient leaves the OR.
Now the virus attaches to the tumor cells and the injection of its RNA begins. The tumor cell is then primed to make the necessary enzyme and die when exposed to 5-fluodouracil. (You can watch a video of how this kind of precision targeting is done, below.)
A really novel way to localize the chemotherapy and minimize its effects on the rest of the body. And the technique might never have been developed without the impetus from HIV.