Hematopoietic cell transplantation (HCT) can be a curative therapy for hematological malignancies as well as refractory autoimmune diseases (i.e. multiple sclerosis, systemic lupus erythematosus, and type 1 diabetes). However, classical HCT requires total body irradiation (TBI)-conditioning of the recipients. The toxicity of TBI-conditioning and the potential for graft versus host disease (GVHD) is limiting the application of HCT in treating the above patients.
The optimal goal of my lab is to develop a radiation-free and GVHD-preventive approach of HCT. We recently reported that a monoclonal antibody, anti-CD3, was successfully used to replace the classical TBI in mouse HCT models, and the new anti-CD3 regimen prevented GVHD. Furthermore, we observed that a successful HCT in newly onset diabetic mice reversed diabetes via re-establishing immune tolerance and re-generation of insulin-producing islet cells.
Although the same procedure did not reverse diabetes in late-stage of diabetic mice, it induced immune tolerance to donor islets, and islet transplantation reversed diabetes. Therefore, the anti-CD3 regimen may represent a new novel approach of HCT. Further investigations will determine the application of anti-CD3 regimen to the treatment of patients.