Every second week of the week in Seattle Children’s Hospital in Washington, a five -year -old child comes by for a fresh dose of genetically modified immune cells, which are administered directly into the liquid around their brain.

The child has been making these visits for more than three years after he has been diagnosed with a devastating form of brain and spinal cord cancer called Diffuse Mittelline Glioma, for which there is no known healing. But the treatment called car-t cell therapy seems to have reduced the tumor and kept under control. With 70 treatments and counting, this five-year-old child may have received more doses of car-t cell therapy than anything else on the planet.

his oncologist Nicholas Vitanza always shines when he talks about the results. Nevertheless, Vitanza is very aware that the child's reaction is unusual. Although several children in Vitzana's clinical study may also have benefited from car-t cell therapy, most reactions were not as dramatic or long-lasting as that of the five-year-old child. The question that Vitanza and others keep awake in his field now is: How can you make this success less a runaway?

on the International Symposium for Pädiatrische Neuro-Onkology in Philadelphia, Pennsylvania , which ended at the beginning of this month, presented Vitanza and other researchers promising early clinical study results that indicated that car-T cells could be effective treatment for fatal CNS cancer.

The studies were designed to test the safety of the therapy, not their effectiveness, and larger studies are necessary to know whether the treatments are useful. In the meantime, the researchers endeavor to optimize their approach to maximize their reach. "We see an insight into a signal," says Jasia Mahdi, a pediatric neurologist at Texas Children’s Hospital in Houston. "Our task now is to find out how we can build on it."

tumor find T cells

Car-T cell therapies consist of immune cells called T cells that have been removed by the recipient and changed so that they produce molecules called chimera antigen receptors (car) on their surface. These T cells are brought back to the body, where their new receptors enable them to recognize and destroy cancer cells.

Despite Persistent security concerns has proven to be successful in the treatment of several types of blood cancer and in some cases Long-lasting remissions of more than a decade . The application of Car-T cell therapies for the treatment of solid tumors as well as those of the brain and the lungs is more demanding. Solid tumors can contain different cells with different mutations and different sensitivities compared to therapy. Solid tumors can also be more difficult to penetrate for the T cells.

Nevertheless, studies on mice have indicated that Car T cells could be effective against diffuse medium line. New therapies for cancer are urgently needed: The standard treatment occasionally consists of radiation therapy in combination with chemotherapy, but the cancer is fatal and the medium survival period is about 13 months after the diagnosis, says Vitanza.

success: a diploma

Now the first clinical studies on car-t therapy against diffuse center line gliomas in children are complete and the results are promising. At the meeting in Philadelphia, Vitanza presented data from a study in which 21 children with diffuser medium-line gli-brain with car-T cells were treated, which attack a protein called B7-H3, which can mainly be found on cancer cells. Only one participant had a strong reaction to the treatment itself, and some live longer than expected, says Vitanza.

Mahdi presented data from a clinical study on T cell therapy that attacks a molecule called GD2. In this study, which was carried out at Stanford University in California, nine people were treated with diffuse center line, and the tumors shrank by more than half.

This study also had a runaway: a young man whose cancer has completely disappeared and who has remained free of cancer for more than 30 months after his first treatment. During this time he completed the high school and now thrives at the university. "All of these normal things mean so much more in this context," says Mahdi. "Otherwise this reality would not have been its."

a menu of options

The researchers strive to extend these dramatic reactions to more of their study participants. Vitzana's team has started another study in which Car-T cells are tested, which attack four different molecules, which can mainly be found on brain and spinal cord tumors, in the hope that T cells that recognize several goals will be more effective.

Another team at the University of California, San Francisco, tests car-T cells that only express the cancer-stemming receptor if the cells are in the central nervous system. The hope is that the T cells are only active where they are needed, which makes them less susceptible to, through "Fagle" Functional, a phenomenon that is known to limit the effectiveness of T cell therapies, says Hideho Okada researched and the leadership of the project is. The team treated their first study participant to an adult with an aggressive brain tumor called Glioblastom , in June and plans to start a similar study in children.

Such modifications of car-t cell therapies are only the beginning, says Vitanza. Researchers are looking for other ways to optimize car-t cell therapies , and in decades, doctors could be able to choose from a variety of options that can be individually tailored to patients. "It is unbelievable that we came to this point," he says. "But in 20 years the car-t cells we use for patients will look very different."