This year will be considered a turning point for the treatment of glioblastoma, a rare and competitive form of brain cancer that carries an average survival time of about 15 to 18 months, said Carl June, a professor at the University of Pennsylvania’s Perelman School of Medicine. and renowned immunologist.
“It’s essentially a death sentence,” says June, who led a team that pioneered the first CAR-T mobile cure to treat certain types of blood cancer. Pediatricians “essentially say, ‘Go home, there’s nothing we can do. ‘”But recent studies, in addition to one conducted in June, have shown promise in the area of mobile infusions of CAR T for the treatment of glioblastoma.
Few people on the planet have replaced the global as profoundly as Carl June. I spoke with him recently about new advances in CAR-T mobile therapy, which works by removing certain immune motifs from a patient, modifying them in the lab to recognize and attack their cancer, and injecting the motifs back into the frame to get the work. do.
June treated the first adult patients with experimental mobile CAR T treatment at UPenn in 2010, and the first pediatric patient in 2012, with amazing results. Five years later, in 2017, the FDA approved T-mobile’s first treatment drug. There are currently six of these drugs approved on the market and approximately 34,000 blood cancer patients have been treated.
“Dr. Cutting-edge studies and technological contributions from June have shown that CAR T mobiles can induce remission and even cure complex cancers, particularly human quality of life and pave the way for a more equitable and equitable world. sustainable for generations over the long term,” said Bruce Levine, a fellow UPenn immunologist who has worked intensively with him for decades. “June’s innovative paintings not only revolutionized the care of patients with hematologic malignancies, but also spurred the emergence of a new industry in the field of CAR T mobile therapy. “
Here are five desirable ideas June shared with me during our discussion:
Treatment features for glioblastoma patients are limited, and no significant innovations have been observed in decades. But a recent trial conducted through a Stanford study organization showed that repeated infusions of CAR T-cells directly into the brains of pediatric patients had benefits. Since then, June’s studies have demonstrated the benefits of direct infusions of CAR-T cells into the brains of adult glioblastoma patients, whose tumors are more confusing than those in children.
“We published six patients about a month and a half ago in an ongoing trial with a dual CAR delivered into the brain,” June said, referring to a T cell treatment that targets two primary antigens expressed through glioblastoma. , to triumph over evasion mechanisms. “And all six patients showed noticeable image adjustments very quickly. ” And she added: “I think in five years we will have FDA-approved CARs for glioblastoma. “
Solid cancerous tumors, which are notoriously more difficult to treat with CAR T treatment than blood cancers. This is because counterfeit tumors have a microenvironment that suppresses immune cells and depletes their potency. June sees hope in so-called “shielded CAR T cells,” which are engineered cells that secrete recombinant proteins to modulate the tumor microenvironment or attack tumor antigens. “You can have a local advantage, but without the systemic responsibilities,” June explained. He is excited about this type of next-generation technique and believes it will be up to CAR T-CARs to tackle counterfeit tumors such as pancreatic cancer or glioblastomas.
In February of this year, a team from a German hospital published information on 15 patients who had been treated with CAR T treatment to treat their lupus, myositis and scleroderma. Patients experienced a 100 percent reaction rate, with remissions lasting an average of 15 months. after follow-up.
More than 10 years ago, “we tried to do it at Penn,” June said, “and we couldn’t do it because our regulatory framework is not Germany’s. “There, a hospital could treat patients on a case-by-case basis with the approval of the local regulatory board, rather than requiring permission from their country’s federal oversight agency.
Since the publication of the German hospital’s remarkable insights, enthusiasm has grown and there are now around 44 international trials recruiting autoimmune patients for CAR T therapy. “This is going to happen,” June said confidently. This exercise has left the station. “
There are two types of mobile therapies. “Autologous” refers to immune mobiles that are extracted directly from a patient’s body and then custom-made with artificial modifications that will allow their own mobiles to fight their express disease. “Allogeneic,” on the other hand, refers to immune motifs that come from a donor. They have pros and cons, and many corporations concentrate on one technique or another.
Proponents of autologous mobile treatment point out that they have a strong history of protection, must be rejected through the patient’s body, and have the ability to persist long-term, at least a decade, by acting as a living drug. However, they are expensive and difficult to manufacture, making them difficult to scale.
Proponents of allogeneic mobile therapy are positive about “commercially available” treatments that can treat patients more quickly and cheaply, even if they carry a higher risk of requiring immunosuppressants. Additionally, they necessarily persist as long as an autologous mobile, which can be a smart thing to do for the right patient.
June says we’ll prefer either approach in the foreseeable long term and that they’ll have independent uses. Cancer treatment, for example, requires the long-term patience of CAR T phones, so autologous phones are a better option. But for autoimmune diseases, allogeneic motifs might be better, because the body only needs them for a few months to reset the immune system: “I don’t think we want an allogeneic motifs to last very long. term, because it is rather an allogeneic mobile. security risk.
Ex vivo refers to the engineering of a patient’s mobile phones outside of their body, which is how all mobile treatments currently on the market are manufactured. Although production is complex and expensive, June says the ex vivo treatment has one very vital advantage: the ability to carry out multiplex genetic engineering on mobiles with base editing and other techniques, allowing scientists to at least 15 genes at a time and metabolically rewire an entire gene. T-mobile.
“I think it will be necessary in some counterfeit tumors,” June said. “And I don’t see that happening in my lifetime with in vivo engineering. “
That said, in vivo engineering, in which a treatment adjusts the patient’s immune motives within their body, is faster, more effective, and more affordable. In fact, the first in vivo mobile treatment trial has just been conducted on patients in Australia through Interius BioTherapeutics.
Capstan Therapeutics, which was co-founded in June and secured my team’s investment in Leaps, is another pioneer in the in vivo mobile treatment of RNA and a proprietary lipid nanoparticle, key technologies in Covid-19 vaccines.
Based on promising preclinical data, Capstan is advancing its candidate lead program toward early clinical evidence of the mechanism.
“Dr. June’s vision is that major advances in nanotechnology and RNA-based medicines have led to existing efforts to open this new bankruptcy in medicine,” said Adrian Bot, chief scientific officer at Capstan. (Disclosure: June owns shares in Capstan, as a co-founder and member of the Scientific Advisory Board. )
We are fortunate to live in an era of immediate medical innovation, where our complicated equipment has the potential to turn devastating diseases into manageable conditions. Beyond autoimmune diseases and fake tumors, the prospects of CAR treatment extend even to regenerative medicine, with theoretical programs for anti-aging therapies, inflammatory dementias, and Alzheimer’s disease.
It is clear that the mobile treatment revolution is just beginning.
Thanks to Kira Peikoff for reporting more and more about this article.
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