Reporter Li Sihui Intern Wang Wucheng
The name "lupus" is derived from the Latin word for "wolf" (Lupus) and "redness" (Erythematosus) - it is named because some patients will have red spots on their faces that resemble wolf bite marks. It is not a simple skin disease, but an autoimmune disease that may affect multiple organs throughout the body.
For a long time, recurrence of the disease and difficulty in stopping medication have been problems that have plagued patients with lupus erythematosus. Li Qiubai's team, professor of the Department of Rheumatology and Immunology at Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology (hereinafter referred to as Wuhan Union Hospital), passed a phase I clinical trial for the first time to verify the feasibility of the CD3×CD19 T cell adapter in the treatment of systemic lupus erythematosus, opening up a new path for the "immune reset" treatment of lupus erythematosus. Recently, relevant research results were published in "Nature Medicine".
The “dilemma” between disease and medicine
Under normal circumstances, the antibodies produced by the human immune system can defend against foreign pathogens, but some antibodies in lupus patients attack the body's own normal cells and tissues. This abnormal immune response may cause rashes, hair loss, joint pain, and even affect multiple organs such as the heart and kidneys.
For a long time, clinical treatment has mainly relied on glucocorticoids and immunosuppressants to control the disease. However, long-term medication may cause adverse reactions such as moon face (shown as facial swelling), hyperglycemia, osteoporosis, infection, etc. In severe cases, the damage caused by the side effects of the medication may even exceed the disease itself.
Li Qiubai told China Science News that he once treated a patient with lupus erythematosus. Due to long-term treatment with high-dose hormones and other drugs, his physical development was seriously affected. The 27-year-old woman still looked like a primary school student. "Looking at it makes people feel heavy."
For many patients, the troubles caused by this disease will extend to marriage, childbirth, employment, and social interactions. Some people reduce or stop taking medications because of fear of side effects, resulting in a recurrence of the disease.
In recent years, belimumab and other biological agents have provided patients with new treatment options, but some patients still need to use immunosuppressants in combination, making it difficult to get rid of the difficulties of long-term medication. The latest CAR-T cell therapy in the world has enabled some patients to achieve long-term "drug-free remission", but its cell preparation process is complex, treatment costs are high, and lymphocyte depletion chemotherapy is usually required in advance, increasing treatment risks.
"Is there a way to achieve a therapeutic effect similar to CAR-T without using chemotherapy, ensuring that the treatment is effective, safe and economical?" With this question, Li Qiubai's team began a several-year exploration of treatment paths.
The “connector” for immunotherapy
At the end of 2022, Li Qiubai, who has been engaged in the diagnosis and treatment of blood diseases for a long time, was transferred to the position of director of the Rheumatology and Immunology Department of Wuhan Union Hospital. Previously, he had been exposed to a new technology used to treat leukemia-T cell adapter in the hematology department. Since this technology can use the body's own immune cells to eliminate tumor cells, can it be used to treat lupus erythematosus?
Li Qiubai introduced that T cells in the human body can identify and eliminate abnormal cells, while B cells are responsible for producing antibodies. The occurrence of lupus erythematosus is closely related to the production of antibodies by B cells to attack their own tissues. How to mobilize T cells to eliminate these B cells has become the key to research.
The CD3×CD19 T cell adapter used by the team is a bispecific antibody. "This antibody is like having two hands." Li Qiubai explained that one end of it grabs the CD3 molecule on the surface of T cells, and the other end grabs the CD19 molecule on the surface of B cells, pulling the two types of cells together, activating T cells, and then eliminating B cells.
Unlike CAR-T therapy, this method does not require the removal of the patient's T cells for in vitro genetic modification. Instead, it directly mobilizes the patient's T cells to function through the injection of antibodies, and does not require lymphocyte depletion chemotherapy in advance.
In 2023, the team completed preparations such as research protocol design and ethical approval. In 2024, it officially started patient enrollment and launched the world's first publicly registered Phase I clinical trial of the CD3×CD19 T cell adapter for the treatment of systemic lupus erythematosus.
After 12 months of follow-up, all 10 evaluable patients reached SRI-4 clinical response criteria, 8 of whom reached lupus low disease activity status, and 6 reached the more stringent clinical remission criteria, and the patient's hormone dosage also decreased significantly.
The hope of “drug-free relief”
"At present, some patients have achieved drug-free remission." Li Qiubai told China Science News that during the continuous observation after the end of the clinical trial, some patients still maintained stable conditions after stopping medication.
The so-called "drug-free remission" means that the patient's disease is relieved without taking treatment drugs. For lupus patients who have long-term dependence on hormones and immunosuppressants, this means the opportunity to get rid of the burden of side effects caused by long-term medication and return to normal life.
The value of this research lies not only in exploring a new drug, but also in opening up a new treatment path. Compared with CAR-T therapy, T cell adapters do not require individualized cell preparation, can achieve standardized production, and adjust the dosage according to the patient's treatment response. This means that it is expected to significantly reduce treatment costs and benefit more patients in the future.
This treatment strategy also provides new research ideas for other autoimmune diseases such as Sjogren's syndrome and rheumatoid arthritis. Li Qiubai said that in the future, he and his team will conduct larger-scale clinical trials and long-term follow-up to further verify the efficacy and safety of this method and explore the application of this treatment strategy in more autoimmune diseases.
At the end of the reporter's interview, Li Qiubai made four suggestions to lupus patients and related parties: First, patients should have confidence in treatment. Lupus erythematosus is not an incurable disease. Through standardized treatment, many patients can return to normal life; second, do not reduce or stop taking medications without permission because of worries about side effects. Adjust the treatment plan under the guidance of a doctor; third, do not believe in some so-called "recipes" and "secret medicines" to avoid causing losses and delaying treatment; fourth, family members, relatives, friends, and society should provide more understanding and care to lupus patients and create a good environment for their normal study, work, marriage, and childbirth.
"Lupus erythematosus sounds scary, but it is actually not contagious and not untreatable. With the development of medical science, it is expected to be completely conquered in the future. I hope everyone will not have fear, prejudice or even discrimination against this disease." Li Qiubai appealed.
