World's First Triple-Target T-Cell Engager Therapy for Refractory Rheumatoid Arthritis

Background

Rheumatoid arthritis (RA) is a chronic autoimmune disease in which the immune system mistakenly attacks the body's own tissues, primarily the joints, causing inflammation, pain, swelling and potential long-term damage. While many patients respond to conventional disease-modifying antirheumatic drugs (DMARDs) and biologic therapies, some develop refractory RA that persists despite sequential use of multiple treatments.

A 32-year-old female patient referred to as Xiao Li had been diagnosed with RA seven years earlier. She had been treated with methotrexate, tofacitinib, baricitinib, adalimumab, an etanercept biosimilar, tocilizumab and other agents, administered alone or in combination. According to the hospital announcement, these efforts resulted in either suboptimal efficacy or side effects, leaving limited conventional options.

What was achieved

On July 1, 2025, the patient received CD2-CD3-CD19 triple-target T-cell engager therapy at the Rheumatology and Immunology Department of Peking University Third Hospital in Beijing. The hospital reported this as the world's first use of this specific triple-target T-cell engager approach in a patient with refractory rheumatoid arthritis. The procedure was performed by the rheumatology and immunology team led by Professor Mu Rong, director of the department.

The hospital stated that the case represents a shift in RA treatment from primarily blocking inflammation toward precise immune repair. Professor Mu Rong's team is leading a global multicenter clinical study of T-cell engager therapies. The study has received approval from China's National Medical Products Administration (NMPA) and the ethics committee and is recruiting patients with refractory RA and systemic lupus erythematosus.

How it works

T-cell engagers are bispecific or multispecific antibody constructs designed to link immune cells. In the CD2-CD3-CD19 triple-target version, the therapeutic molecule uses a specific antibody structure to simultaneously engage receptors on the surface of T cells (CD2 and CD3) and the CD19 marker expressed on pathogenic B cells.

This bridging directs the patient's own circulating T cells to recognize and precisely eliminate the disease-contributing B cells located in inflamed tissues. According to the hospital, the approach aims to clear pathogenic cells and help rebuild a balanced or "correct" immune response. In contrast to broad systemic immunosuppression, the targeted mechanism is described as potentially reducing infection risk while supporting longer-term therapeutic effects and, in some cases, the possibility of drug-free remission.

What it means for international patients

Peking University Third Hospital maintains an International Medical Service (IMS) that supports patients with services in English, Korean and Japanese. The service provides access to specialist consultations across the hospital's clinical departments, including through hotlines and appointment systems. The Rheumatology and Immunology Department conducts clinical research, including the ongoing multicenter T-cell engager study.

International patients considering care for refractory RA or participation in related studies should contact the hospital directly to verify current availability, determine individual eligibility according to the approved protocol, and obtain full details on requirements. Suitability for any specific therapy, including experimental approaches, must be assessed by the treating physicians. No claims regarding outcomes for international patients are reported in the sources.

About the hospital

Peking University Third Hospital (also known as PKU Third Hospital or Beiyi San Yuan) is located at 49 Huayuan North Road, Haidian District, Beijing. Founded in 1958, it is a comprehensive tertiary Class A (Grade 3A) public hospital directly administered by the National Health Commission and affiliated with Peking University. It integrates medical services, teaching, research, prevention, rehabilitation and health management. The facility has more than 2,700 beds.

In 2025 the hospital recorded more than 5.9 million outpatient and emergency visits, 198,000 inpatient admissions and 117,000 surgical procedures, with an average length of stay of 4.16 days. It has received A++ ratings in national performance evaluations of tertiary public hospitals for multiple consecutive years and was selected in 2022 as one of 14 national pilot hospitals for high-quality development of public hospitals. It lists 27 national key clinical specialties (or construction projects), notably including sports medicine (the designated medical center for Chinese Olympic Committee athletes), reproductive medicine (site of mainland China's first IVF birth in 1988), orthopedics, ophthalmology, gastroenterology, obstetrics and gynecology, and cardiology.

The hospital's Rheumatology and Immunology Department was formally established in 2006, maintains 30 inpatient beds, handles approximately 70,000 outpatient visits per year, and has ranked in the top 20 in China for scientific and technological influence (STEM metrics) in rheumatology and autoimmune diseases. The department offers specialized clinics and participates in multiple clinical trials. The International Medical Service offers one-stop outpatient and inpatient support for foreign patients.