A cold virus genetically modified to infect only cancer cells and stimulate the immune system response has performed well in a small clinical trial involving 12 children suffering from a type of incurable brain tumor.
The results are modest but important, since they provide the greatest improvement compared to current treatments that has been seen so far, explains Marta Alonso, a researcher at the University Clinic of Navarra and co-author of the study, who is published today in the prestigious medical journal New England Journal of Medicine. The publication itself dedicates its editorial to this research, highlighting the new avenues of research that it opens up.
The study focused on diffuse intrinsic trunk glioma, which develops in the brain and is the most lethal tumor in children. It is such a rare disease that it is considered abandoned, since new treatments are hardly pursued. Currently these patients do not have any effective drug and the median survival is 12 months. “Right now there is nothing to give these patients; in fact, the modest improvement in survival that we have obtained, with an average of 17.8 months, is the best result that has ever been obtained in a clinical trial of this type”, Alonso points out. In two patients, survival was as long as three years, he adds. The work provides some hope for new treatments that may 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 the MD Anderson Cancer Center (USA). In 2018, it showed good results in adults suffering from glioblastoma, the deadliest brain cancer. That same year, Alonso received a prestigious aid of two million euros from the European Union to investigate these viruses as immunotherapy for children. In part, this public funding has made possible the development of the current clinical trial, which has required significant doses of research and genetic sequencing in the laboratory and which did not have the support of the pharmaceutical industry.
The DNX-2401 carries two genetic modifications. The first makes it bind selectively to integrins, proteins that are abundant on the surface of tumor cells. The second only allows it to replicate and cause an infection if the retinoblastoma gene is activated, a typical marker of cancer that is absent in healthy cells.
The doctors took biopsies of the tumors of the 12 patients, a recent diagnostic practice that was not usually practiced for fear of leaving brain lesions, but that provides great information about the genetic profile and vulnerabilities of 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 causes hardly any side effects. In addition, a delay in tumor expansion has been observed. It seems that the virus not only eliminates part of the cancer cells, but also provokes a reaction of the immune system that begins to identify and eliminate the tumor cells. The approach is similar to that already used in the main cancer immunotherapy drugs, but in this case using viruses and not antibodies.
Physicians and researchers from several Spanish hospitals, as well as from other countries, including Fueyo and Gómez-Manzano, have participated in the study. Those responsible hope to start a second phase of trials in 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 effectiveness of these modified pathogens in combination with already approved immunotherapy drugs.
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