Study of the Week: CAR-T Cell Therapy for Autoimmune Diseases?

Welcome to Study of the Week from Patient Worthy. In this segment, we select a study we posted about from the previous week that we think is of particular interest or importance and go more in-depth. In this story we will talk about the details of the study and explain why it’s important, who will be impacted, and more.

If you read our short form research stories and find yourself wanting to learn more, you’ve come to the right place.


This week’s study is…

Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus

We previously published about this research in a story titled “CAR-T Cell Therapy for Lupus and Other Autoimmune Conditions?” which can be found here. The study was originally published in the scientific journal Nature Medicine. You can read the abstract of the study here

This research team was affiliated with the Friedrich Alexander University Erlangen-Nuremberg.

What Happened?

As the fields of oncology (the study of cancer) and rheumatology (the study of immune-system related diseases of the joints, bones, etc.) have developed, they been able to successfully borrow approaches from one another to help make new breakthroughs. As an example, scientists have found that certain methods that target the immune system can help treat certain types of cancer. Now, scientists are learning that some of these same techniques can be used for autoimmune diseases, such as lupus.

An advanced form of cancer treatment that has been developing in recent years is CAR-T cell therapy. Often used for cancer that has developed resistance to other treatments, this method involves extracting immune system cells (T-cells) from the patient, modifying them to target cancer cells in the lab, and then reintroducing them into the patient’s body. In this study, researchers used CAR-T cell therapy that targeted CD19, a protein that on the surface of B-cells, which are the most prevalent immune system cell that produces the autoantibodies found in lupus.

Five patients (one male, four female) were authorized to receive the treatment for the study under compassionate use protocols. These patients did not respond to several widely used immune-suppressing therapies. Treatment with CAR-T cell therapy was able to induce remission in these patients. One patient has been symptom-free for 18 months without requiring any other treatment; another has had the same result for 12 months. 

Following the treatment, new B-cells appeared after 100 days, leading the researchers to wonder if disease symptoms would resume; but they did not. The new B-cells were not producing autoantibodies like the old ones were. In cancer, CAR-T cell therapy is often considered a last resort due to serious side effects, but they were not nearly as bad in the lupus patients; their immune systems were not destroyed and the main side effect was mild cytokine release syndrome.

About Systemic Lupus Erythematosus

Systemic lupus erythematosus, more commonly known simply as lupus, is an autoimmune disease that is characterized by a red facial rash. An autoimmune illness is one in which the body’s own immune system begins to damage healthy tissue. Certain drugs can induce the disease, but it is most commonly caused by a combination of certain genetic variants, which, when exposed to an environmental trigger, can cause symptoms to begin. Symptoms of lupus include facial rash, swollen, painful joints, fatigue, fever, swollen lymph nodes, chest pain, hair loss, and mouth ulcers. Women are more frequently affected than men. The disease tends to appear in a relapsing-remitting pattern of symptoms. Its symptoms are often vague at first, making diagnosis of lupus more difficult. Treatment may include avoiding sunlight, immune system suppressing drugs, and pain medication. Most people with lupus are able to control their disease effectively without overall lifespan being affected. To learn more about systemic lupus erythematosus, click here.

Why Does it Matter?

The remarkable performance of CAR-T cell therapy in these patients, who had been living with severe, treatment-resistance lupus, was a surprise to scientists:

 “We were really surprised how effective it was. I have to say that blew us away.” – Georg Shett, study leader

While other immunosuppressants can target B-cells, CAR-T is capable of doing so more thoroughly, even reaching into the bone marrow and lymph nodes. Of particular note is that despite the durable remission produced by the treatment, the B-cells that returned did not start producing autoantibodies and cause symptoms to resume; in effect, the treatment was able to “reset” the patients’ immune systems.

“This would seem to be the holy grail of treatment.” – Mark Leick, physician, Hematopoietic Cell Transplant and Cell Therapy Program at Massachusetts General Hospital.

A much larger scale trial with more patients will be needed to help confirm these encouraging findings. These preliminary results could also have implications for other autoimmune diseases that involve the B-cells, such as multiple sclerosis or scleroderma. If CAR-T cell therapy can be this effective in lupus, then there’s a chance it could be useful for these conditions as well.

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