Editorial: Finding New Hope in Old Treatments: Repurposing Immunotherapy in Transplantation

Yeqi Nian¹Jasper Iske^2*Xiaodong Yuan^3*

• ¹Department of Kidney Transplantation, Tianjin First Central Hospital, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
• ²Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum der Charité (DHZC), Berlin, Germany
• ³Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

novel agent that attenuates alloimmune responses when combined with standard therapy. Clinical applications and patient-specific scenarios further bring the promise of repurposing to life. A recent clinical trial provides compelling evidence supporting the repurposing of the anti-CD38 antibody felzartamab-originally developed for multiple myeloma-for the depletion of plasma cells and mitigation of antibody-mediated rejection, with a favorable safety profile [3] . In the setting of transplant complications, Xiong et al. report the successful off-label use of baricitinib, a JAK1/2 inhibitor approved for rheumatoid arthritis, to manage life-threatening steroid-refractory chronic graft-versus-host disease, offering a new therapeutic avenue for this challenging condition. Furthermore, Kong et al. review the pressing need for agents that provide both immunosuppressive and anti-tumor effects, discussing the dual potential of mTOR inhibitors and chemotherapeutic drugs such as capecitabine in transplant recipients with oncological risk factors. The development of non-genotoxic conditioning regimens is also critical, particularly in hematopoietic stem cell transplantation. Okalova et al. discuss how monoclonal antibodies and antibody-drug conjugates may replace traditional alkylating agents or irradiation, potentially reducing the risks of secondary malignancies and organ toxicity. The collective work in this Topic underscores that drug repurposing is not merely about finding new uses for old drugs; it is a strategic inquiry into the universality of immunological principles. By mining the rich landscape of approved immunotherapies, the transplant community can accelerate the development of precise, effective, and safer regimens. The studies presented here-spanning bioinformatics discovery, mechanistic validation in models, and proof-of-concept clinical trials-chart a course for this integrated future. We hope this collection inspires continued collaboration across immunology, oncology, and computational biology to overcome the enduring barriers in transplantation and improve long-term outcomes for recipients worldwide.