Doctors often say that lupus affects no two patients alike. This disease causes abnormalities in the immune system and can attack almost any organ in the body, but it is very difficult to tell when and where it occurs. A patient may have lesions on the face, Comparable to being bitten by a wolf Written by a 13th century physician who gave lupus its name. Another patient may have kidney failure. The other thing is the fluid around the lungs. But what doctors can tell all their patients is that they will have lupus for the rest of their lives. The origins of these autoimmune diseases are often shrouded in mystery, and the immune system, which treats the body we live in as an enemy, never fully relaxes. Lupus cannot be cured. Autoimmune diseases cannot be cured.
However, two years ago, study Something came out of Germany that challenged all these assumptions. Five patients with uncontrolled lupus went into complete remission after undergoing a repurposed cancer treatment called CAR T-cell therapy, which nearly wiped out malignant immune cells. The first patient treated has been symptom-free for nearly four years. “We haven’t had the courage to think about how to treat the disease,” says Anka Askanase, a rheumatologist at Columbia University Medical Center who specializes in lupus. However, these amazing results – remission in all patients – have inspired a new wave of optimism. 40 people or more Lupus patients around the world are now receiving CAR T cell therapy, and most go into remission without the use of drugs. It is too early to declare that any of these patients will be cured for life, but it now appears to be within the realm of possibility.
Beyond lupus, doctors hope CAR-T heralds major advances against autoimmune diseases with increasing prevalence. alarming rise. CAR-T is already in experimental use. treat the patient with other autoimmune diseases such as multiple sclerosis myositisand myasthenia gravis. And the success of CAR-T has led researchers to borrow other (cheaper and easier) strategies from cancer treatments to kill failing immune cells. Not all of these ideas will work, but if they do, the next few years could mark a turning point in the treatment of some of the most frustrating and intractable diseases of our time.
CAR-T cell therapy independently developed As a way to kill malignant cells in blood cancers. Scientists later reasoned that it could also be used to kill certain white blood cells called B cells that go wrong in certain autoimmune diseases. One group tried a CAR-T-like treatment for an autoimmune disease called CAR-T. pemphigus vulgarisand another CAR-T against lupus. It worked, but these experiments were only done in mice.
This was the total amount of scientific evidence available at one point in time. 20 year old female She visited her doctor in Erlangen, Germany, and asked him to try something for her severe and uncontrollable systemic lupus erythematosus. None of the long-term medications typically used to manage lupus were effective. Her kidneys, heart, and lungs all failed, and she could only walk 30 feet on her own. CAR-T was dangerous, doctors agreed, but the lupus was killing her.
CAR-T cell therapy could essentially turn her immune system against itself. First, doctors extracted a type of immune cell called a T cell from her blood and manipulated it to create chimeric antigen receptor T (CAR-T) cells that can recognize and destroy her lupus-causing B cells. Created. CAR-T cells can cause dangerous and overwhelming symptoms inflammatory response Her doctors worried that CAR-T could have a similar effect on patients with autoimmune diseases whose immune systems are already in overdrive. “We take T cells and activate them like crazy and attack T cells that are massively overactivated in activated autoimmune diseases. So when you think about it, why would you do that? That’s a bit crazy, isn’t it?” says Fabian Müller, a hemato-oncologist at Erlangen University Hospital and one of the doctors on the German team that pioneered the treatment. Fortunately, the woman with lupus had no serious side effects, and neither did any other patients the German group subsequently treated.. They all lead daily lives with no lupus symptoms or medication. Mueller said the woman who could only walk 30 feet now runs five times a week. She is considering going back to school and getting a master’s degree in immunology.
Muller and his colleagues believe that CAR T-cell therapy works by removing enough B cells to cause a “deep reset” of the immune system. CAR-T cells are tenacious little assassins. They can even find and destroy B cells hidden deep within the body’s tissues. The patient’s B cell count eventually recovers, but the new B cells no longer mistakenly attack the body itself. Cancer patients are sometimes considered “cured” after treatment. 5 year remissionAnd the first lupus patient to receive CAR-T is not far from that milestone. But this treatment doesn’t eliminate the genetic predisposition that makes many patients susceptible to the disease, says Donald Thomas, a rheumatologist in Maryland. It will take time to know whether the remission is durable enough to actually be a “cure.”
Still, these astonishing results have sparked a gold rush among biotech companies eager to solve autoimmune diseases. CAR-T start-up companies founded for the purpose of cancer treatment, Focus on targeting autoimmune diseases. And major pharmaceutical companies, etc. bristol myers squib, AstraZenecaand Novartis We are developing our own treatment methods. Columbia University’s Askanase is currently an investigator on five separate trials using CAR-T or similar cell therapies, and he hears from more companies all the time. Interest is so high that “we don’t even know if there will be enough patients” to try new treatments, she said. About 1.5 million Americans Some people have lupus, but clinical trials target only a minority of them, those with the disease enough to warrant experimental treatment but not enough to cause irreversible organ damage. Only.
Currently, CAR-T for lupus and other autoimmune diseases is only available in the United States through clinical trials, which effectively means that nearly all lupus patients do not have access to CAR-T. . Jonathan Greer, a Florida rheumatologist, works in a seven-physician practice that treats hundreds of lupus patients. Not a single person is receiving CAR-T. He is not aware of any centers operating in Florida to conduct these studies, so interested patients would have to travel out of state.
Even if FDA-approved for autoimmune diseases, CAR-T is a slow and expensive process. Because each patient’s own cells are reengineered, it cannot be easily scaled up. CAR-T for cancer costs approximately $500,000. Patients also need chemotherapy to kill existing T cells to make room for CAR-T, which increases risk. Lupus usually requires tapering of drugs to control the disease, which can lead to flare-ups. All these complications make current CAR-T repeat therapy suitable only for lupus patients with severe disease who have run out of other options.
The practical limitations of CAR-T have long plagued the cancer field, and researchers are already coming up with ideas to get around them. Many of the simpler strategies for killing B cells are now being applied to everything from blood cancers to autoimmune diseases. They include using donor T cellsdifferent types of immune cells called natural killer cellsor molecules that bind to B cells with the goal of destroying T cells. those molecules called Bispecific T cell engagerBiTE is “cheap, fast and easy,” but may not penetrate as deeply into tissues where B cells reside, Mueller said. Nevertheless, in September, New England Medical Journal Successfully published two books case report A method called BiTE has been described as successfully treating a small number of autoimmune diseases, including lupus. teclistomab. Similar commercially available BiTES could also be repurposed for autoimmune diseases.
Even these simple treatments may ultimately be “sufficiently effective,” Askanase said. And while its ease of use may ultimately trump custom CAR-T therapies, it is unlikely that the treatment will reach all of the millions of lupus patients worldwide. It’s simply too expensive and cumbersome. Other cutting-edge treatments Initially, it was approved with much fanfare. Even if CAR-T itself was never widely adopted for autoimmune diseases, CAR-T opened the door to new ideas that could one day revolutionize treatment.
