Islet Transplantation in Type 1 Diabetics Using an Immunosuppressive Protocol Based on the Anti‐LFA‐1 Antibody Efalizumab

• Published in: American journal of transplantation Vol. 10; no. 8; pp. 1870 - 1880
• Main Authors: Posselt, A. M., Bellin, M. D., Tavakol, M., Szot, G. L., Frassetto, L. A., Masharani, U., Kerlan, R. K., Fong, L., Vincenti, F. G., Hering, B. J., Bluestone, J. A., Stock, P. G.
• Format: Journal Article
• Language: English
• Published: Malden, USA Blackwell Publishing Inc 01-08-2010; Wiley
• Subjects: Adolescent; Adult; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal, Humanized; Antilymphocyte Serum - therapeutic use; Biological and medical sciences; Blood Glucose - metabolism; Clinical islet transplantation; Diabetes Mellitus, Type 1 - surgery; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; immunoregulatory T lymphocytes; immunosuppressant therapy; Immunosuppression Therapy - methods; Islets of Langerhans Transplantation - methods; Lymphocyte Function-Associated Antigen-1 - administration & dosage; lymphocyte trafficking; Male; Medical sciences; Middle Aged; Mycophenolic Acid - therapeutic use; prednisone‐free immunosuppression; Sirolimus - therapeutic use; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Tacrolimus - administration & dosage; Tissue, organ and graft immunology; type 1 diabetes mellitus; Endocrinopathy; Immunopathology; type 1 diabetes mellitus; Antipsoriatic agent; Langerhans islet; Homograft; prednisone-free immunosuppression; Autoimmune disease; Clinical islet transplantation; Monoclonal antibody; Efalizumab; Lymphocyte function associated antigen 1; Immunomodulator; Immunosuppression; immuno-suppressant therapy; lymphocyte trafficking; Type 1 diabetes; Graft; Immunosuppressive agent; immunoregulatory T lymphocytes; Endocrine pancreas
• ISSN: 1600-6135; 1600-6143
• DOI: 10.1111/j.1600-6143.2010.03073.x

The applicability of islet transplantation as treatment for type 1 diabetes is limited by renal and islet toxicities of currently available immunosuppressants. We describe a novel immunosuppressive regimen using the antileukocyte functional antigen‐1 antibody efalizumab which permits long‐term islet allograft survival while reducing the need for corticosteroids and calcineurin inhibitors (CNI). Eight patients with type 1 diabetes and hypoglycemic unawareness received intraportal allogeneic islet transplants. Immunosuppression consisted of antithymocyte globulin induction followed by maintenance with efalizumab and sirolimus or mycophenolate. When efalizumab was withdrawn from the market in mid 2009, all patients were transitioned to regimens consisting of mycophenolate and sirolimus or mycophenolate and tacrolimus. All patients achieved insulin independence and four out of eight patients became independent after single‐islet transplants. Insulin independent patients had no further hypoglycemic events, hemoglobin A1c levels decreased and renal function remained stable. Efalizumab was well tolerated and no serious adverse events were encountered. Although long‐term follow‐up is limited by discontinuation of efalizumab and transition to conventional imunnosuppression (including CNI in four cases), these results demonstrate that insulin independence after islet transplantation can be achieved with a CNI and steroid‐free regimen. Such an approach may minimize renal and islet toxicity and thus further improve long‐term islet allograft survival.
An immunosuppressive regimen based on the anti‐LFA‐1 antibody efalizumab showed some promising results in eight islet transplant recipients.
See Editorial by Oberholzer et al 1725.