Four people with extremely aggressive brain cancer lived up to 50% longer than expected thanks to a personalized experimental vaccine, according to results published this Wednesday by the Spanish biochemist Hector Mendez and his colleagues at the University of Florida, in the American city of Gainesville. The patients, now deceased, suffered from glioblastoma – the most common malignant tumor in the brain – in a terminal phase when they voluntarily participated in the clinical trial. “It’s quite promising,” says Méndez, born in Salamanca 42 years ago and settled in the United States.
The human body’s defenses often do not recognize cancer cells as a threat. The Florida team employs a sophisticated strategy. Researchers inject lipid particles measuring millionths of a millimeter into a vein, with genetic information obtained directly from each patient’s tumor. This messenger RNA recipe, like that of the Pfizer and Moderna vaccines against covid, trains the immune system to think that tumor cells are dangerous viruses and destroy them.
Méndez explains that patients with standard treatment, used as a reference, had a survival of six months. One of the vaccinated people, however, reached nine months, 50% more. Another participant lived eight months, 33% longer. In the other two patients, the results were positive, but not so positive, says the Spanish biochemist. The team, led by the American oncologist Elias Sayour, wants to now start a larger trial, with 24 patients, to confirm the safety of the vaccine and refine the dose. The next step would be another trial with about 25 children with glioblastoma.
“It seems to improve people’s survival and we have not found any type of chronic toxicity so far,” celebrates Méndez, trained at the University of Salamanca and the Cajal Institute in Madrid. Previous animal experiments were also promising. A dozen dogs with fatal brain cancer lived an average of almost five months after receiving the vaccine, multiplying the usual survival of one or two months. The new results are published this Wednesday in the specialized magazine cell.
The oncologist Laura Angelats she applauds the new work, but is cautious. “It is a very innovative strategy and the preclinical data are very interesting, but we still have very little data in patients to be able to confirm that it is a safe and effective treatment,” emphasizes the expert, from the Hospital Clínic, in Barcelona.
There are two other experimental RNA vaccines in advanced human trials. The oncologist Vinod Balachandran is leading testing of a pancreatic cancer shot at Memorial Sloan Kettering Cancer Center in New York. And pharmaceutical companies Moderna and Merck have also obtained promising results with an RNA vaccine against melanoma. All of them are therapeutic vaccines, to treat an already established cancer. English oncologist Sarah Blagden, from the University of Oxford, is leading a project to develop a preventive vaccine against lung cancer, based on harmless chimpanzee cold viruses, a technology similar to that of the AstraZeneca vaccine against covid.
Angelats recalls that glioblastomas are “cold tumors,” because inflammatory or immune system cells barely appear around the cancer cells. Immunotherapy, which involves stimulating one’s own defenses against cancer, is much less effective in cold tumors. The oncologist highlights that, if the experimental vaccine against glioblastoma finally works, the same strategy could be applied against other cold tumors, such as colon cancer. “There is a lot left, but it is promising data,” she celebrates.
The immunologist Luis Alvarez Vallina He also praises the new work. “I find it very interesting, it is one more step towards the coming of age of RNA vaccines, which are going to be very important against cancer. This is a relevant contribution, despite its limitations,” says the scientist, head of the Clinical Research Unit in Cancer Immunotherapy at the 12 de Octubre Hospital and the National Cancer Research Center, in Madrid.
Álvarez Vallina highlights that the lipid nanoparticles used by the American team are larger than usual and have a multi-layered structure, like an onion, which increases their alert effect on the immune system. The immunologist predicts a future with combined strategies, such as vaccination accompanied by other types of immunotherapy, such as immune checkpoint inhibitors. “The scenario is going to be very plastic, depending on the characteristics of each patient and her clinical situation, but I believe that vaccines are going to become an important element of the arsenal,” he maintains.
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