Viruses as therapy: This is the revolutionary Spanish treatment that seeks to use the common cold to combat brain cancer.

Research into potential cancer treatments perhaps requires an extra dose of creativity. It is, without a doubt, a disease that poses unique challenges: after all, how do you combat a disease in which our own cells cause the damage, and which not even our immune system recognizes as a threat?

The truth is that in recent years, there have been very encouraging advances in this regard, and our country is playing a leading role in the development of pioneering treatments. This is the case of the clinical trial recently conducted by Dr. Álvaro Lassaletta, pediatric oncologist at the Niño Jesús University Children's Hospital; his work has demonstrated the safety of an innovative therapy based on modified viruses for treating medulloblastoma, one of the most aggressive childhood brain tumors.

"It's a very novel idea"

As Lassaletta explains in an interview with 20minutos , this study, funded by the CRIS Cancer Foundation, used oncolytic viruses transported by mesenchymal cells, a formula called Alocelyvir: "At Niño Jesús, we have been working with oncolytic viruses for 20 years. Manuel Ramírez Orellana and Javier García Castro's team developed a common cold virus (an adenovirus) genetically modified so that it only attacks tumor cells. To reach them, we used a vehicle, which are mesenchymal cells: from previous studies, we know that they go where there is inflammation and tumor cells."

This technique has already been tested on many types of cancer with good results, he specifies. "It's a very novel idea," Lassaletta affirms, "although it has a certain history. Here in Spain, Dr. Marta Alonso, from the University Clinic of Navarra, has developed it in a very important way; worldwide, treatments of this kind are being developed and are even already being used for some adult tumors in specific circumstances."

However, until now, its use in brain tumors had not been attempted: "A few years ago I wanted to see if the treatment, called celyvir, could work on brain tumors. To do so, we conducted a pilot study with some compassionate use cases (outside of a clinical trial) and found it to be safe; then we conducted two clinical trials."

"Patients didn't experience many side effects: just a slight fever on the day the virus was infused and sometimes a headache."

"In one of them, the tumor is a diffuse invasive brainstem tumor (DIPG), the deadliest brain tumor there is," he continues. "In this trial, funded by the Vicky's Dream Foundation , we included six patients, and it helped us confirm the drug's safety and see that the patients didn't have many side effects (a little fever on the day the virus is infused and sometimes a headache)."

"And then we conducted the same trial with patients with medulloblastoma, the most common malignant brain tumor in children and adolescents; it has a good prognosis , as it is cured in 70% of cases, but the remaining 30% relapse; that's why we included six patients with medulloblastoma relapse who had received other treatments before the virus."

A difficult start

Lassaletta's team quickly encountered some difficulties. "We began the trials with an MRI that showed us the progression of the tumor," he explains. "Celyvir uses mesenchymal cells from the patients themselves, extracted from their bone marrow; but we saw that, having been treated with many therapies before, they were sometimes damaged. Furthermore, the process requires six weeks, and the start of treatment can be delayed: with this type of cancer, you can't afford to wait that long. So we decided to switch to using donated (allogeneic) mesenchymal cells, and that's why this treatment is called Alocelyvir."

In fact, the initial impressions weren't good. "Alocelyvir was administered once a week for eight weeks, without any additional treatment. In the tenth week, we performed another MRI, and we saw tumor progression in all the patients, so we thought the treatment was useless and removed them from the trial to receive other therapies."

"However," the doctor adds, "it was later that we saw that these patients had very long survival times with treatments that we know typically don't work well. Some have survived more than two years, and one is still alive after that time; therefore, what we saw in that second MRI wasn't actual progression, but rather inflammation of the tumor due to the action of the virus itself." In this regard, he clarifies that "certain immunotherapeutic treatments, as in this case, produce inflammation that can be difficult to distinguish from tumor progression."

"We are already working on the next clinical trial."

Lassaletta believes the clinical trials have met their objective. "These initial trials were Phase 1B trials, so they were really meant to test safety. And we've seen that they are safe, as they have very few side effects." Furthermore, he adds, "we've seen that the virus has an immune effect: it signals tumor cells so the patient's immune system can attack them."

Still, he cautions that more research is still needed on the issue. "Although the results are promising, we haven't proven anything yet," he says. "But we're already working on the next clinical trial , which will include an even larger number of patients. It will thoroughly study the efficacy and use against other malignant brain tumors."

It should be clarified that this system isn't necessarily expected to achieve a miracle cure . As the expert reveals, the goal is rather to achieve improvements in survival compared to current options and to have less harmful alternatives, as many of the techniques currently in use have serious side effects. "Of course, we're looking for more effective treatments against the recurrence of these tumors," he explains, "but also, in the future, we're trying to avoid treatments with such high toxicity as radiotherapy."

"We don't yet know if it's possible to achieve complete remission. These are very innovative treatments."

"We don't yet know if it's possible to achieve complete remission," he insists. "These are very novel treatments , and we also need to test combinations, for example, with chemotherapy or other immune therapies." He concludes: "Now, we need to see which patients respond, which patients don't, and why, and what we can combine the treatments with to make them more effective."

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