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Leukemias and brain tumors are the types of cancer more frequent in kids. The latter, moreover, are the ones with the highest mortality at this stage. And of these, the diffuse intrinsic glioma of trunkwith an incidence of 30-40 cases per year in Spain, is deadliest of all. There is no cure. Radiation therapy is applied as palliative treatment. Survival in this disease is about 12 months. A devastating diagnosis. Now, scientists from the University Clinic of Navarra and Cima have opened up a hopeful way to treat this ailment with a virus modified to attack cancer cells and activate the immune system.
The results of this clinical trial, which have been published in the latest issue of the ‘New England Journal of Medicine’, show that it is a feasible and safe procedure.
In its editorial, the publication highlights the novel nature of oncolytic virus treatment for this type of tumor and underlines the importance of having carried out a small study with a well-selected population.
“As the tumor is in the brainstem cannot be operated. Only biopsies are done and not in all centers. Palliative radiotherapy is given so as not to lose quality of life, but it is not curative, which is why it is so necessary to find new treatments that address it, ”explains Dr. Marta Alonso, co-author of the study and director of the Laboratory of Advanced Therapies for Tumors, to ABC Salud. Pediatric Solids of the Cima and the University Clinic of Navarra.
Diffuse intrinsic truncal glioma is a random tumor. There are no predisposing factors. Although it can appear at any time in childhood and adolescence, there is a peak incidence at 7 years and another at 18. “It is thought that the peak coincides with two moments of brain development, at 7 and 18. It is as if it were a developmental error, very rare. The development program is wrong and gives rise to tumors”, explains Dr. Alonso.
Until recently, this childhood cancer was hardly studied. But in the last decade, says the doctor, there has been a very strong movement driven by affected families to seek funding and make researchers and society aware of the need to find new treatments. «I spent a lot of time in adult brain tumors and through this study I came into contact with childhood brain tumor. I decided that when I had my laboratory I wanted to dedicate myself to this. He was working with oncolytic viruses. We began studying the possibility of transferring them to this type of tumor. We carried out studies with cells and animals, we saw that the virus was effective and safe and that allowed us to make the leap to the phase 1 trial that we are now publishing”, says the co-author of the work.
The study has been carried out in 12 children, between 3 and 18 years old, with a recent diagnosis of diffuse intrinsic truncal glioma, from Spain and other European countries, who had not yet started treatment with radiotherapy. The test consisted of inject an oncolytic virus into the tumor developed in the laboratory of doctors Juan Fueyo and Candelaria Gómez-Manzano, from the MD Anderson Cancer Center in Houston.
“Its about adenovirus 5, one of those that causes the common cold. Two things are modified to make it tumor specific. A piece of protein is cut so that, although it infects normal and tumor cells, it only replicate and kill tumor cells. The way it infects is also changed so that it binds to receptors that are more highly expressed on tumor cells. In this way they are sent signals to the immune system that something is wrong so that he comes to help. The virus is injected into the tumor through a biopsy,” explains Dr. Marta Alonso.
The objective of the phase I trial was to demonstrate the therapy safety, which they have achieved. The only adverse effects detected are those related to having an adenovirus (cold): headache, fever, nausea, but all of a mild nature. But, in addition, they have seen that this treatment, together with radiotherapy, has achieved a survival up to 17.8 months. «The fact of finding something that has moved the survival rate up already opens a door, a path to follow. There are 12 patients, it is a small sample. Until we are able to heal, joy is contained and there is no need to cast bells, but open a door of hope», says the co-author of the study.
The next steps will be to try to extend this phase 2 or multicenter trial to get this treatment approved for this type of tumor. In the laboratory, says Dr. Alonso, they will continue to improve the therapeutic tool so that the virus “remains safe but more effective.” And for that, they need financing. This clinical trial of an academic nature -not linked to industry- has been financed by contributions from donors, a project of the European Research Council (ERC-Consolidator, awarded to Dr. Alonso) and by the University Clinic of Navarra itself, which has considered the essay of general interest.
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