More and more studies give hope for the effectiveness of CAR-T therapies in solid tumors previously considered incurable. A group of scientists from Stanford University (United States) launched a clinical trial in 2020 with 11 patients diagnosed with diffuse midline glioma, a tumor that affects the nervous system, with a very poor prognosis and which appears in children and young people. The results, published this Wednesday in the magazine Nature, are encouraging: the treatment made it possible to obtain a complete remission of the disease in one of them, aged 17. The patient has not had any detectable pathology for four years. In addition, the tumor reduced its volume between 52 and 91% in three other cases and in the majority there was a “neurological benefit”, according to the researchers.
The work, far from being definitive – it is currently a phase I trial – “is very promising as a suggester of effectiveness,” says Manel Juan, head of the immunology department at Hospital Clínic from Barcelona, in statements to the Science Media Center. This opens the door to the manufacture of a disease that is currently incurable thanks to a treatment that “can last and integrate into the body because it is a living drug, unlike chemo or radiotherapy , which only act for the duration of their application,” he explains.
CAR-Ts are personalized therapies based on the reprogramming of immune system cells to attack tumor cells. Their cost is high, but the Spanish public health system is starting to produce them in its own hospitals at a significantly lower price to treat blood tumors, where the evidence for their effectiveness is stronger.
Experts receive the results of the trial, rigorous and well designed despite the small number of patients, as a “real boost to this immunotherapy in terms of safety and effectiveness”, in the words of Luis Álvarez-Vallina, director of the Cancer Immunotherapy Unit of the 12 de Octubre University Hospital and the National Cancer Research Center.
However, it is important to measure the aggressiveness of this tumor. Although signs of improvement were observed, these did not prevail in the majority of patients. The trial began with 13 people: two of them were discharged early due to the rapid progression of the disease, and by 30 months after the first infusion, only two of the remaining 11 people had survived. They were on average 15 years old.
Diffuse midline glioma is associated with symptoms that were significantly reduced during the trial. For example, the patient who responded best – to the point where the disease regressed – had “sensory and motor deficits” that required him to use a wheelchair. After receiving treatment, her motor coordination improved “to the point of becoming independent.” Another 30-year-old patient, whose tumor shrank by 90% at the best time, presented, before the first infusion, “severe paraplegia, neuropathic pain and intestinal and bladder dysfunction”. The pain improved, as did the function of his extremities. He was able to walk with a cane.
Few cases and very selected
One of the problems with this treatment, like other cancer treatments, is toxicity. This study demonstrates, several experts agree that there is a route of administration – directly into the central nervous system – that is less toxic and more effective. “The most interesting thing about the study is that intracavitary locoregional administration (in the same area where the original tumor is located) is the way to go. Thanks to this intratumoral route of administration, the performance of CAR-T cells against solid tumors can be optimized with maximum exposure,” analyzes Ignacio Melero, professor of immunology at the University of Navarra and researcher at CIMA.
The work, however, has limits. There are few cases treated and only one of them obtained a complete response after four years; In addition, “the patients were highly selected so that they were in good functional condition and had tumors of adequate size,” emphasizes Marta María Alonso, researcher at the Solid Tumor Program of CIMA and Clínica University of Navarra. The researchers themselves admit that it is still “difficult to determine whether GD2-CAR T cell therapy has a favorable impact on overall survival” with such a small and selected sample. and “should be evaluated in future phase II trials.”
