First clinical trial in Korea uses CAR-T cell therapy to treat intractable lupus

For the first time in Korea, a clinical study has begun to treat systemic lupus erythematosus using immuno-oncology CAR-T cell therapy. Lupus is a typical chronic autoimmune disease that occurs when the immune system, which is supposed to protect the body from invading pathogens, instead attacks the body itself. Lupus—derived from the Latin word for "wolf"—was named because the skin rash was thought to resemble a wolf bite. The exact cause of the disease remains unknown, and its symptoms are diverse, as reflected in the saying, “It has a face of a thousand colors.”

Seoul St. Mary's Hospital said on Tuesday that Professors Joo Ji-hyun and Lee Bong-woo of the Rheumatology Center and Yoon Jae-ho of the Hematology Department began the first clinical study in Korea in March to administer CAR-T cell therapy, a type of immuno-oncology drug, to a female lupus patient in her 40s who did not respond to standard treatment and had no other options.

According to the hospital, the patient was diagnosed with systemic lupus erythematosus after developing systemic edema and proteinuria during pregnancy in 2009. After giving birth, she was treated with high-dose steroids and several immunosuppressive drugs, but her lupus nephritis did not reach remission. Instead, she developed avascular osteonecrosis as a side effect of prolonged high-dose steroid therapy. Proteinuria and declining kidney function persisted despite multiple immunosuppressive treatments. If left untreated, lupus-induced kidney damage could accelerate and progress to end-stage renal failure requiring hemodialysis.

Her attending physician, Professor Joo, decided to try CAR-T cell therapy based on the medical evidence that the indications for CAR-T cell therapy have been expanding to autoimmune diseases overseas. She applied to the Ministry of Food and Drug Safety for a clinical trial of the drug for the treatment of lupus patients.

Seoul St. Mary’s Hospital also collaborated with a blood hospital to provide multidisciplinary care. Although rheumatic and hematologic diseases share some immunologic overlap, collaborative or joint treatment has been rare due to differences in target patient groups.

However, the hospital’s extensive experience with CAR-T cell therapy for patients with relapsed or refractory large B-cell lymphoma and B-cell acute lymphoblastic leukemia has proven valuable in the CAR-T treatment process for the lupus patient, according to the hospital.

Over the last 14 outpatient visits since the infusion in March, the patient has maintained her daily routine without experiencing any acute side effects and has shown improvement in lupus-related markers—such as proteinuria, complement levels, and anti-DNA antibodies—even after discontinuing immunosuppressive drugs.

In the early stages of lupus, patients may present with fever, generalized weakness, depression, extreme fatigue, weight loss, a butterfly-shaped skin rash across the bridge of the nose, or arthritis in the hands or wrists. However, the disease requires aggressive treatment if it leads to major organ damage, such as to the kidneys.

The use of aggressive immunosuppressive agents is being driven by studies showing that combination therapies are more effective at improving patient outcomes than monotherapy.

CAR-T cell therapy is an immuno-oncology treatment in which T cells (immune cells) are extracted from a patient's blood, genetically modified to express chimeric-antigen receptors (CARs) that target specific antigens on cancer cells, and then reintroduced into the patient's body. To date, CAR-T cell therapies have been used to treat blood cancers such as leukemia and lymphoma.

Through this mechanism, CAR-T cell therapy has been shown to suppress B cells, which play a key role in the pathogenesis of lupus, making it a potential treatment for the disease. Studies conducted overseas have demonstrated that lupus patients who did not respond to conventional treatments have been successfully treated with CAR-T therapies, leading to symptom improvement and remission of lupus disease activity.

“It is significant that we can treat patients with intractable lupus, which could have progressed to chronic kidney failure, using CAR-T cell therapy—proven to be safe and effective in hematologic diseases,” said Professor Yoon. “We will continue to do our best to treat difficult cases by participating in multidisciplinary care.”

"Although the 10-year survival rate for lupus patients receiving immunosuppressive drugs has recently been reported to be as high as 90 to 95 percent, some patients may experience life-threatening lupus involvement of major organs such as the lungs, heart, kidneys, and brain," said Joo. "Beginning with this clinical trial, we will expand our research to help patients with refractory lupus who have not responded to existing treatments and have no other options."