At the end of last year, at the American Society of Hematology Annual Meeting in San Diego, Dr. Fabian Müller from the University of Erlangen-Nuremberg in Germany presented a set of latest research data: 15 patients with autoimmune diseases experienced a rebirth after receiving CAR-T cell therapy, with the first group of treated patients maintaining a disease-free status for over two years.
Multiple sclerosis is a disease where the immune system attacks nerve cells. Antibodies (orange) bind to nerve cells (blue), summoning immune cells to that site.
Image Source: American Fun Science Website
Antigen-presenting cells (right) sometimes train T cells (left) not to launch an attack.
Source: Scientific Image Database
According to a recent report on the website of the British journal Nature, after decades of attempts, this result has sparked hopes for the complete cure of autoimmune diseases such as diabetes, lupus, and multiple sclerosis.
CAR-T Therapy Shows Significant Effectiveness
For over 50 years, researchers have been trying to "tame" cells that trigger autoimmune diseases such as diabetes, lupus, and multiple sclerosis. Most approved therapies currently work by suppressing the body's entire immune response, which often alleviates symptoms but increases the risk of infections and cancer for patients. Therefore, scientists have been exploring various approaches in an effort to cure these diseases and restore people to a healthy life.
The CAR-T therapy used by Müller et al. is a leading example of this effort.
CAR-T therapy utilizes immune cells called T cells. Researchers first extract T cells from the patient's body, genetically engineer them to produce chimeric antigen receptors (CARs), and then reintroduce the modified CAR-T cells into the patient's body.
As early as 2021, Müller's team began using this method to treat a 20-year-old female patient with systemic lupus erythematosus, and her condition quickly improved without significant side effects. This was the world's first trial of CAR-T therapy for systemic lupus erythematosus patients.
In the study mentioned above, the team genetically modified T cells taken from patients outside the body to carry antibodies that recognize the CD19 protein on "rogue" B cells. The results showed that 44 days after CAR-T cell administration, the patient's antibodies disappeared, her condition improved, and there were no significant side effects.
Subsequently, Müller et al. continued their efforts, and the symptoms of 15 autoimmune disease patients (8 with systemic lupus erythematosus, 4 with systemic sclerosis, and 3 with idiopathic inflammatory myopathy) were significantly improved or even completely resolved.
Professor Carl June, a pioneer in CAR-T cell therapy, commented in the journal Cell that although CAR-T cell therapy for lupus still requires larger-scale studies and longer-term follow-ups to confirm, this therapy does hold great promise.
Similarly, scientists at Magdeburg University in Germany successfully treated myasthenia gravis using CD19-targeted CAR-T cell therapy.
More Precise B Cell Clearance
Nature reports that CAR-T therapy targets and kills all B cells, but most autoimmune diseases are caused by only a small fraction of B cells. Dr. Amy Payne, a dermatologist at Columbia University in the United States, sought a method to selectively target these "culprits."
Payne studied a rare skin disease called mucous membrane pemphigoid, in which the immune system mistakenly interprets the body's own BP180 protein as "foreign" and produces antibodies to attack it. The current standard therapy for pemphigoid is monoclonal antibodies, which destroy B cells. As B cells disappear, antibodies targeting BP180 also disappear, leading to symptom relief in patients, but this therapy is currently inefficient.
Payne hopes to improve traditional CAR-T cell immunotherapy by selectively killing B cells that cause autoimmune diseases without harming the rest of the immune system. To achieve this, Payne's team designed an artificial receptor that guides the patient's T cells to only eliminate harmful B cells containing BP180. This artificial receptor is called a Chimeric AutoAntibody Receptor (CAAR), and this therapy is also known as CAAR-T therapy.
The research team pointed out that compared to traditional CAR-T technology, CAAR-T technology is less prone to off-target effects, effectively treats autoimmune diseases, and avoids side effects caused by off-target effects. Currently, the team is testing this therapy in patients with pemphigoid and myasthenia gravis.
Payne believes that T cells are the "celebrities" in the field of immunology, while B cells are like the "underdogs" hiding in the halo of T cells, but perhaps B cells are the "main characters" after all.
Rise of "Reverse Vaccines"
According to a report from the American website Fun Science on September 25 last year, Professor Jeffrey Hubbell, a tissue engineering professor at the University of Chicago, and his team have developed a new type of vaccine that selectively suppresses the immune system instead of activating it.
Researchers used the vaccine on mice with a condition similar to multiple sclerosis. The results showed that the vaccine reversed the symptoms in mice and restored the function of nerve cells.
Anokion, a company co-founded by Hubbell, has initiated clinical trials to test whether this reverse vaccine can help patients with multiple sclerosis and celiac disease. The company has completed phase I trials for multiple sclerosis patients and is currently recruiting participants for phase II trials to evaluate its efficacy.
Lawrence Steinman, a neuroimmunologist at Stanford University, is also developing a new "reverse" DNA vaccine for multiple sclerosis, targeting a protein in the brain that mimics a part of the Epstein-Barr virus, which may be a trigger for multiple sclerosis. In addition, in 2021, scientists from BioNTech and the University of Mainz in Germany reported that they had developed a tolerance-inducing mRNA vaccine that can suppress symptoms of multiple sclerosis in mice.
(Original Title: Dawn of Hope for Curing Autoimmune Diseases)
