Fifteen years ago two Spanish neurologists developed a new treatment against glioblastoma, the most lethal type of brain cancer. It consisted of a catarrh virus genetically modified to selectively make the tumor cells sick.
After a long investigation of years the compound developed by Juan Fueyo and Candelaria Gomez-Manzano began to be tested experimentally in patients a few years ago and the preliminary results are promising , especially because it manages to stop tumors for which there is no effective treatment.
Now, another Spanish scientist, Marta Alonso, has received a prestigious grant from the European Union of two million euros to support her research with these viruses in cases of childhood brain cancer, a group of diseases that can be considered abandoned by the industry. They are rare and there are hardly any funds to investigate possible treatments.
Alonso, a researcher at the University Clinic of Navarra, is part of the team that has launched the first clinical trial with glioblastoma adults who are given a single dose of DNX-2440, the new oncolytic virus version developed by Fueyo and Gomez-Manzano in the USA.
“Conventional immunotherapy works by eliminating the brakes that have the lymphocytes that prevent them from fighting the tumor cells, instead this virus does step on the accelerator so that the destruction of the tumor is faster,” explains Alonso.
The virus has three genetic modifications that make it more effective when it comes to fighting brain tumors. The first one makes it bind to integrins, abundant proteins in tumor cells. Second causes the virus to be activated only if the retinoblastoma gene is deactivated, another marker characteristic of cancerous tissues.
The third modification causes that when the cells of the immune system are launched to fight the virus, it promotes the production of OX40L, a protein that allows the cells of the immune system to identify the tumor cells and eliminate them.
“In this way we bring virotherapy closer to immunotherapy,” explains Juan Fueyo, neurologist at the MD Anderson Cancer Center in the US “The OX40L activator expresses in the membrane the cells infected by the virus, so when a lymphocyte touches it, it activates, calls more lymphocytes and destroys the tumor, New virus is 10 to 100 times more powerful than the previous one and that is due to its ability to activate the immune system, “he explains.
The European Research Council has just announced that Alonso is one of the 291 recipients of a Consolidator Grant, a prestigious financial aid for scientists in the middle of their careers. The two million euros will allow Alonso’s team to start a clinical trial in children with different types of brain and nervous system tumors with DNX-2440 if the results of tests with adults show low toxicity and are promising.
This treatment is still in the first phase tests of the three necessary, with which it is not yet known if it can become a commercial treatment. The initial results with the previous model of the virus and those of the first adult patient treated with the new one are promising, says Alonso.
“Childhood brain tumors are very rareso there is no interest from the pharmaceutical industry in developing treatments, which is a problem given the high mortality of some of them, “explains Alonso.
The biologist explains that in addition to starting the clinical trial in children her team will continue to analyze the specific characteristics of childhood tumors in search of new proteins similar to the OX40L but more specific. “The immune system is changing throughout life and is not the same as a baby that of a teenager.
One of the things we want to do is find new ligands that increase the effectiveness of viruses without increasing toxicity, “explains Alonso. If all goes well, this new type of immunotherapy could become a conventional treatment in about four or five years, he explains.
“These treatments make sense,” says Antonio Pérez, pediatrician expert in oncology at the La Paz Hospital in Madrid. “The problem is the local inflammation generated by these treatments, but it is a promising strategy in a field where little progress has been made beyond radiotherapy and surgery,” he adds.
This type of European aid is very competitive, only 12 of every 100 scientists who show up get it. In total, 16 researchers in Spain have received one of the ERC’s grants. The countries that have obtained the most are the United Kingdom (55), Germany (38), France (32), Switzerland (29) and Israel (23). Spain is the seventh country that receives the most scholarships this year.
Also in the field of cancer, the project of Arkaitz Carracedo, researcher at the CIC Biogune Research Center in Bilbao, has been selected. His project focuses on the study of the evolution of prostate cancer. “The tumor cell lives and grows in hostile terrain throughout its existence, and develops adaptive mechanisms to persist over time.
Like living things in nature, tumors also suffer from a natural selection process that makes only the best adapted cells survive. Therefore, if we understand which are the most relevant adaptations for these cancer cells, we could develop treatments aimed at blocking them, so that the tumors are extinguished, “explains the scientist in a press release from his institution.