Marta Alonso, left, with other members of her team at the University Hospital of Navarra.CUN
A cold virus genetically modified to only infect cancer cells and stimulate the immune system’s response has performed well in a small clinical trial in 12 children suffering from a type of incurable brain tumor.
The results are modest but important because they offer the greatest improvement seen so far compared to previous treatments, explains Marta Alonso, researcher at the University Hospital of Navarra and co-author of the study, published today in the prestigious medical journal New England Journal of Medicine. The publication itself dedicates its editorial to this research and highlights the new research avenues it opens.
The study focused on diffuse intrinsic trunk glioma, which develops in the brain and is the deadliest tumor in children. It is such a rare disease that it is considered abandoned as new treatments are rarely pursued. Currently, these patients have no effective medication and the median survival time is 12 months. “Right now there is nothing to give these patients; In fact, the modest improvement in survival we achieved, averaging 17.8 months, is the best result ever obtained in a clinical trial of this type,” emphasizes Alonso. Two patients survived for up to three years, he adds. The work offers hope for new treatments that could one day cure these tumors, possibly in combination with other drugs.
The treatment used is the adenovirus DNX-2401, developed more than 15 years ago by neurologists Juan Fueyo and Candelaria Gómez-Manzano, researchers at MD Anderson Cancer Center (USA). In 2018, it showed good results in adults suffering from glioblastoma, the deadliest brain tumor. In the same year, Alonso received a prestigious €2 million grant from the European Union to study these viruses as immunotherapy for children. In part, this public funding has enabled the development of the current clinical trial, which required significant research effort and genetic sequencing in the laboratory and was not supported by the pharmaceutical industry.
The DNX-2401 carries two genetic modifications. The first causes it to bind selectively to integrins, proteins that are abundant on the surface of tumor cells. The second only allows it to replicate and cause infection when the retinoblastoma gene is activated, a typical cancer marker absent in healthy cells.
Doctors took biopsies of the 12 patients’ tumors, a newer diagnostic practice not usually practiced for fear of brain lesions, but which provides great information about the genetic profile and susceptibility to cancer in each of the patients. Once the biopsies were obtained, the virus was injected into the tumor site.
The results show that the treatment is safe and hardly causes any side effects. In addition, a delay in tumor expansion was observed. It seems that the virus not only eliminates part of the cancer cells, but also provokes an immune system response that begins to identify and eliminate the tumor cells. The approach is similar to that already used with the main cancer immunotherapeutics, but in this case viruses are used and not antibodies.
The study involved doctors and researchers from several Spanish hospitals, as well as from other countries, including Fueyo and Gómez-Manzano. Those responsible hope to be able to start a second phase of studies on patients in 2023. At the same time, Alonso’s team is working on new, improved versions of the same virus. One of the most promising avenues is to study the efficacy of these modified pathogens in combination with already approved immunotherapeutic agents.
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