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Zika's fears collapsed last year. New cases of the disease in the Americas for nearly two years and hundreds of thousands of infected people are extremely rare these days. However, that does not mean that doctors have suddenly forgotten everything. And in the process of developing and testing a functional vaccine capable of protecting against the virus, new research suggests that we may have found a cure for one of the most deadly forms of cancer that threaten humans.
In the new results published in the journal mbio A team of researchers from the University of Texas Medical School in Galveston and China has successfully used a Zika vaccine currently under development to kill glioblastoma, an extremely aggressive form of brain cancer that kills most patients in less than two years. the cancer that recently killed Senator John McCain. Less than 3% to 5% of patients live in the last five years and, even if treated with surgery followed by high doses of radiation and chemotherapy, cancer usually returns because of the strange ability of glioblastoma stem cells to hide
"The truth is that if you remove the non-stem cells, which could account for up to 98% of the cancer, they can all come back," says Andrew Sloan, neuro-oncologist at Case Western Reserve University School of Medicine. . .
The pathology of the Zika virus (caused by the ZIKV virus) causing brain damage in the fetus makes it an attractive candidate weapon against glioblastoma. "ZIKV targets normal stem cells in the developing fetal brain, but has minimal effects on the adult brain," says Milan Chheda, neuro-oncologist at the University of Washington in St. Louis. interactions with glioblastoma. It turns out that ZIKV particularly likes to target neural stem cells that have not yet become fully formed neurons. The brain of a growing fetus obviously contains a lot of them. "Since stem cells from glioblastoma share the properties with neural stem cells, we wondered whether the natural and lytic break-in [or rupturing] The activity of ZIKV could be exploited to target and kill cancer stem cells.
Although the intentional injection of a person with an illness as a medical treatment – virotherapy – may seem risky and dangerous, researchers have long worked on the development of viruses as a disease. ############################################################################# 39, cancer control agents. "The use of viruses as a form of cancer treatment has potential," says Justin Lathia, a researcher at the Cleveland Clinic's Lerner Research Institute, who was not involved in the study. "The main benefits are the ability of the virus to simultaneously kill tumor cells and activate the immune system. But a major disadvantage is the ability to control viral replication. These approaches could still have untargeted effects "and essentially turn the virus into healthy cells in the body.
Chheda and his colleagues had published results last year that showed that Zika, in its normal state, could target and kill glioblastoma tumor cells in vitro. And when they were injected with Zika, mice with glioblastoma lived two to three times longer than without treatment, while non-cancer cells remained intact.
Pei-Yong Shi, a UTMB geneticist who worked on this study, decided to go further and see if a safer form of Zika could achieve the same kind of results without risking an infection . So, he and other colleagues turned to the ZIKV-LAV vaccine, which uses a live form of the attenuated virus to prevent infection with the Zika virus, in order to provide immunity to the strains of Typical Zika.
The team tested this vaccine on mice raised without an immune system and found that it did not cause infection and did not damage the brain of the host or n & # 39; 39, did not lead to behavioral problems. More importantly, the researchers also tested the vaccine on mice grafted with one of two types of glioblastoma tumor lines from human patients. The vaccine has been successful in globally reducing tumor growth and specifically targeting and killing the cancer stem cells of both tumor lines, extending the median rodent lifespan from 30 days to 48 days and from 31 days to 53 days, respectively. .
The results are very encouraging, but we are still far from having successfully used Zika to eliminate the deadliest form of brain cancer. First of all, tests on mice are never equivalent to tests on humans, and this study itself was not a typical mouse study. "These results are obtained in the absence of an intact immune system, so it's hard to know how the immune system would be altered, potentially in a positive way to reduce tumor growth," Lathia notes. .
Sloan echoes these concerns, pointing out that often, the other goal of virotherapy is to prime the immune system so that it targets the tumor itself. "The problem in this mouse model, he says, is that if you activate the immune system too much, there may be inflammatory effects that damage or kill the patient."
We still do not know the exact mechanism by which ZIKV causes infection and spreads through the body and as long as we do not characterize these processes and will not have strong means to prevent transmission, even if it is an attenuated form of the virus. As the authors of the study write, "to succeed, an oncolytic virus must strike the right balance between efficacy and safety." It's often difficult to find.
"Although I think this has exciting potential, and I'm encouraged," says Sloan, "I would not put patients on this point yet."
However, given the deadly nature of glioblastoma, it is likely that many patients will try their luck and choose a Zika-based treatment, even with a risk of infection. There are few good options for patients, and any treatment that may reduce tumor resurgence and prolong survival certainly deserves to be explored.
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