Oncolytic Virus Targets Three Brain Tumors

Every year, between 1,300 and 1,500 minors are diagnosed with cancer in Spain, according to the Spanish Registry of Childhood Tumors (RETI-Sehop). A diagnosis for which no child and no parent is prepared.

Leukemias, brain tumors and lymphomas are the most common, despite how rare they are. Thus, childhood cancer affects 138 children for every million children under 15 years of age.

20% of new diagnoses are tumors of the central nervous system. Its annual incidence in minors is about 5 cases per 100,000. Despite the advances made in their diagnosis, treatment and follow-up, in general, the prognosis of these very aggressive tumors remains unfortunately gloomy.

In order to shed some hope, the Dr. Jaime Gállegocoordinator of the Central Nervous System Tumors Area of the Cancer Center Clínica Universidad de Navarra (CUN)and his team are finalizing the details to be able to start as soon as they receive authorization from the European Medicines Agency (EMA) a Phase 2 trial to treat pediatric brain tumors using a modified virus. The oncolytic virus they will use will be “an adenovirus, serotype 5, that causes common colds,” explains the researcher, but not before specifying that they work with this oncolytic virus with which researchers Marta Alonso and Ana Patiño began working 15 years ago.

They will not use the original virus, but a version of it, a genetically modified virus through bioengineering that they will inject directly into the tumor of children and young people without effective alternatives. Hence the name. Virus with the ability to destroy tumor cells.

«Al virus – Gállego highlights – we have made two changes. One of them is for replicate only in tumor cellswhich have genetic alterations that healthy cells do not have and the virus only replicates with that genetic alteration, and another so that has more affinity in the infectivity of the virus to tumor cells», that is, increasing the ability of the infectious agent to invade the host (in this case, the tumor cell) and multiply in its tissues.

«We inject the virus into the tumor and these tumors are not a homogeneous mass, but rather have healthy brain tissue and what the virus does is infect the tumor cells and also the healthy cells. But with this modification it has greater adhesion by the tumor cells, the membrane proteins of the tumor cell surface,” adds the researcher. In other words, when the modified virus enters the body, it will infect the tumor cell, where the virus will divide, causing the tumor cell to die. On the other hand, the virus will enter healthy cells, but it will respect them due to the modifications made to the virus.

What will it consist of?

This research continues the clinical trial published in 2022 in “The New England Journal of Medicine” in which for the first time internationally, pediatric patients with diffuse intrinsic trunk glioma were treated with an oncolytic virus, demonstrating that the procedure was feasible and safe, and after being tested in different clinical trials in rodents over the last 15 years.

But in this phase 2 the modified virus will be used against three groups of pediatric brain tumors: high-grade gliomas, embryonal tumors, such as medulloblastomas or the atypical rhabdoid teratoid tumor, and ependymomas. Three types of tumors for which the effectiveness of the oncolytic virus has already been proven in an experimental animal model.

«In this phase 2 will recruit 15 patients, expandable to 39 between 1 and 25 years of age. We will start with five patients for each of the three tumor groups and if in one of those five patients we see that we stop the disease or generate a positive response (a reduction of the tumor), We will expand up to 13 patients in that group and the same in each group of patients by type of tumor,” Gállego says.

«All patients will be newly diagnosed, not like in the previous phase 1 clinical trial in which the participants were patients in refractoriness (lack of response) or progression after receiving chemotherapy and radiotherapy,” highlights the doctor.

As for the method, as the researcher explains, what they will do is inject a cannula, a very fine needle, directly into the tumor with the diluted modified virus, helped by 3D neuronavigation in order to decide where to put the tip of the needle. so that the journey is not harmful to the brain, thus avoiding functional areas.

An intervention that will have been previously planned with a resonance to have every detail well thought out.

Asked about side effects, Gállego explains that in the phase 1 trial “there was no significant toxicity. In that trial carried out on 12 children we saw signs of efficacy: a significant response and longer than normal survival, although unfortunately we did not cure them. Now this phase 2 will allow us to confirm the safety that we have already demonstrated and evaluate whether it is truly effective.”

As for why it is not injected into the blood, Dr. Gállego explains that “otherwise the immune system would eliminate the oncolytic virus in five minutes.”

The next step will consist of incorporating a new genetic edition to the virus to further stimulate the immune system, so that, in addition to killing tumor cells, trigger an immune response against the tumor. That is, “turn on the immune system switch,” says Gállego.

While waiting for the EMA to give them the green light, once the trial starts, it “will last approximately three years, although it may possibly last less because recruitment is expected to be rapid because these patients have no alternatives.

“The trial is not yet open,” Gállego emphasizes. «The families tell us that they want to have a chance to fight and there still isn’t one. But it will be very soon,” he confides.

One million euros from the AECC

And it is urgent. «We need effective treatments. They have already demonstrated the role of this oncolytic virus in phase 1 against glioma and now the range is opening to more brain tumors,” highlights Marta Puyol, scientific director of the Spanish Association Against Cancer (AECC)an entity that participates in the financing of the phase 2 trial with one million euros through the “AECC 2025 Clinical Studies Grant”.

“We must promote pediatric clinical trials that are top-of-the-line so that patients are allowed to participate from the beginning because in the end that is where innovation is,” Puyol emphasizes.

“It is also important that there are trials aimed at the pediatric population because many times what is done is to do trials for the adult population and if the results are good, adjust doses by weight for minors and that is not innovating and it also does not always work,” he adds.