Poliovirus for the treatment of glioblastoma: details

Polio versus brain tumor

Alexandra Bruter, Polit.<url> based on the materials of Duke University:
Targeting Cancer with Genetically Engineered Poliovirus (PVS-RIPO)

Scientists from Duke University (USA) began to look for volunteers and announced a fundraising campaign for the first phase of clinical trials of a new method of glioblastoma therapy.

Glioblastoma is an extremely aggressive brain tumor. This is a relatively rare disease, it does not respond well to therapy. Even under the most favorable circumstances, no more than 15% of patients live more than five years from the moment of diagnosis.

There are several reasons that make glioblastoma treatment difficult. Firstly, brain cells die easily and regenerate very poorly. Exposure to chemotherapeutic drugs or radiation, which can kill all the tumor cells, will kill a lot of ordinary neurons for the company. Secondly, just because of its fragility, the brain was reliably separated from the rest of the body by a blood-brain barrier. This barrier does not allow pathogens of infections, potentially toxic substances, etc. to penetrate into the brain, but it is not yet possible to explain to the barrier that this particular potentially toxic substance is a cure for a deadly disease, therefore, from the whole set of drugs for chemotherapy, you can choose only a few that can penetrate the barrier themselves.

There are some people who are still alive, although they were first diagnosed 10 or even 20 years ago, but in the vast majority of cases, after surgical removal of the tumor, they relapse over time and lead to death. Radiotherapy and chemotherapy in general are considered as a palliative in themselves. In general, the state of affairs today is so sad that a complete cure is rarely talked about, and a good result of therapy is considered to prolong the life of patients after diagnosis (without treatment, the median survival rate is 4.5 months).

One of the promising areas for the development of new treatment methods is attempts to force your own immune system to fight the tumor more actively. Actually, she has her own methods of fighting tumors, and a tumor can grow and develop successfully only if she has found a way to deceive her. Otherwise, the immune system will destroy the tumor embryo, consisting of one or more cells, and the person will not even know about it. Apparently, such events are not so rare in the human body.

But what if the antitumor immunity has already been deceived? The essence of the work of scientists from Duke University is to use antiviral immunity against tumor cells. Poliovirus, a virus that causes polio, was chosen as an immune activator. This virus is convenient because it has a tropism to the cells of the nervous system in advance, that is, it prefers to infect them.

To prevent the drug from being comparable in danger to the disease, the authors of the work modified the virus by replacing its own regulatory elements with regulatory elements of the rhinovirus that causes colds.

On the schematic image of the modified PVS-RIPO virus
part of its protein shell is not shown, but in its cavity
yellow indicates the poliovirus' own DNA,
pink – rhinovirus DNA – VM.

As a result, the virus could not actively multiply in all cells, could not cause symptoms of polio. During the 10 years of the study, there have never been any cases of its transformation back into a normal polio virus.

The created virus turned out to be very successful. There are more polio virus receptors on the surface of malignant cells than on the surface of ordinary neurons, so the virus mainly infected tumor cells. Secondly, suitable biochemical conditions for the reproduction of the virus were also found only in tumor cells, so only they died after infection, and ordinary cells remained alive. And, finally, thirdly, infection of tumor cells with a virus led to the activation of the immune system and its active fight against the tumor.

The therapeutic method has demonstrated good results in animal experiments, and in 2012 the FDA allowed to switch to human studies. Since then, five patients have received the medicine, four of them are still alive. Considering that we are talking about patients with recurrent tumors, this is a pretty good result.

 The case of a girl, the first participant of the experiment, is especially noteworthy. Her treatment began in May 2012, the symptoms of the disease began to recede, and are currently absent. Nine months after the start of treatment, the girl returned to school and now feels well. Tomography shows a decrease in the tumor.

Along with clinical trials of the method of combating glioblastoma, the authors plan to apply it, possibly modifying it, for the treatment of other malignant diseases.

Portal "Eternal youth" http://vechnayamolodost.ru 07.04.2015