CAR-T therapies, the great hope against brain cancer: "There is an urgent need for treatments."

Cancer poses a very particular enigma for medicine: How do you fight a disease when the body itself is damaging itself? So far, scientists have not come up with a single, definitive answer; however, in trying to meet the challenge, they have devised truly ingenious strategies. And, to date, few are as promising as CAR-T therapies.

CAR-T treatments consist, in a nutshell, of extracting immune cells from the patient , modifying them to fight the tumor (or even other diseases), replicating them in the laboratory, and reintroducing them into the body. It's a relatively new procedure, but it's already bearing fruit: in Spain, a country that has strongly invested in this strategy, they are already being administered through the public health system to patients with hematological cancers.

"It's still a very new therapy."

The potential of CAR-T therapies is not limited to blood tumors, and there are projects seeking to apply the idea to even more difficult-to-treat cancers. This is the case of Drs. Ricardo Gargini and Berta Segura Collar , respectively head and co-head of the translational neuro-oncology laboratory at Hospital 12 de Octubre in Madrid. As they explain to 20minutos , one of their current lines of research involves the application of CAR-T therapies to solid brain tumors.

"The project is in the preclinical phase, and the idea is to finally begin a clinical trial within about three years with the most appropriate target for this type of tumor using the CAR-T strategy," Segura explains. "What we're doing is launching that clinical trial , with regard to the preclinical validation required for the drug agency to allow us to use CAR-T in patients," Gargini adds. "As it's still a very novel therapy, we need to establish baseline clinical parameters and obtain safety and toxicity data."

That is to say, for now, the studies being conducted use in vitro cultures of tumor cells from patients and animal models (mice), as a preliminary step to transferring this possible use of CAR-T therapies to the clinic.

"It is an individualized treatment"

"CAR-T therapy," Segura explains, "is an individualized treatment for each patient. Blood cells are removed from each patient, leaving only the T cells, a type of immune system cell responsible for ultimately attacking tumors."

"A system is implanted [in the brain tumor] that introduces modified cells. Then, with very specific monitoring, we can see how it evolves."

And he continues: "So, what we do in the laboratory is modify them in such a way that they are capable of recognizing the tumor that the patient has and attacking it in a much more effective way. Once this has been done, they are injected back into the patient; in this case, we would do it directly intratumorally , in the head."

Gargini adds more details: "During the surgical procedure, a system would be implanted that would introduce these modified cells. It will be possible to monitor the entry of the modified cells, and with very specific patient monitoring, we will be able to see how the tumor evolves over the course of days or months."

"It's going to have a lot of future in any tumor."

This application of CAR-T represents an advance compared to the typical use of the strategy today, which is in the setting of hematological tumors. "It's almost a scientific leap forward," Gargini assesses. "Hematological cancers have shown a good response, and Hospital 12 de Octubre is a pioneer in this regard, especially in the case of myeloma, which has been treated here in patients with good results. The challenge is that CAR-T therapy has so far only achieved partial responses in solid cancers, unlike what happens with blood tumors; and, furthermore, accessing brain tumors is particularly difficult due to the surgical procedure involved and because the organ is very sensitive to inflammatory and toxic processes."

"There are many aspects we've been working on to establish the correct application parameters , in order to achieve real efficacy in the development of this CAR-T therapy," he continues. "It's something our laboratory is pioneering, but the challenges are enormous."

"Our CAR-T therapy would be applicable to a wide variety of patients , and we intend to extend it to young adult patients along with the other type of glioma (one of the main brain cancers), which is pediatric glioma. But the current focus of our study is on adult glioblastomas," he explains.

Berta Segura, for her part, states that "this therapy has great potential for any type of tumor , since in our body for any cancer in any tissue the cells that are capable of finally finishing it off are the T cells. The key is to see for each type of tumor how we have to 'educate' them so that once they return to the patient's body they are more effective."

"It's a therapy that will have a great future for any type of tumor," he assures. "But it's very complex: tumors have many pathways to survive, and when you attack one, they develop others."

"Brain tumors require extra monitoring"

When dealing with diseases with such a high mortality rate as cancer, it's necessary to resort to treatments that can have significant risks or side effects . Ultimately, it's about balancing the benefits and harms.

CAR-T therapies are no exception to this calculation and can have significant adverse effects, although over time, scientists are making them increasingly safer.

"The development of any potentially harmful alteration is closely monitored, so it practically no longer poses a problem."

"There has been a lot of progress thanks to its use in hematological studies," says Gargini, "and there is a lot of control at the different risk points, such as the possibility of inducing another type of cancer through the modification of T cells. At the medical level, very specific monitoring is done for the development of alterations in these cells that could be harmful, so it practically no longer poses a problem."

"With regard to brain tumors in particular, additional monitoring is required , with much more exhaustive patient follow-up. Hospital 12 de Octubre has the resources to do this, with experts in CAR-T neurotoxicity, which is the most difficult aspect to control," he adds.

"There is an urgent need for new therapies"

Gargini believes that "it is important to publicize these new therapies that are beginning to be clinically evaluated," and acknowledges "the support of Hospital 12 de Octubre, which is helping tremendously to make this possible for patients. We are pioneers in Spain in being able to achieve this. Also important is the support from the pathology and hematology departments, which are essential for ensuring clinical control. It is the multidisciplinary contribution that can lead to these types of extremely complex therapies."

In turn, Segura emphasizes "the importance of being able to test this type of therapy on brain tumors , since they are the most aggressive, with an average survival rate of just one year. In the last 20 years, there has been little progress in therapeutics, despite the fact that many types of treatments have been tested. There is a very urgent need for a new therapy for this type of patient."

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