Phase I (Safety) Study of Autologous Tolerogenic Dendritic Cells in Type 1 Diabetic Patients
| Autor: | David N. Finegold, Jo Harnaha, Massimo Trucco, Brett E. Phillips, Nick Giannoukakis |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent Emerging Treatments and Technologies Endocrinology Diabetes and Metabolism Population medicine.disease_cause Transplantation Autologous Autoimmunity Young Adult 03 medical and health sciences 0302 clinical medicine Immune system Double-Blind Method Internal medicine Internal Medicine medicine Humans Insulin education Original Research 030304 developmental biology Immunosuppression Therapy Advanced and Specialized Nursing 0303 health sciences Type 1 diabetes education.field_of_study Hematology business.industry Dendritic Cells Dendritic cell Middle Aged medicine.disease 3. Good health Transplantation Diabetes Mellitus Type 1 Immunology Female business Ex vivo 030215 immunology |
| Zdroj: | Diabetes Care |
| ISSN: | 1935-5548 0149-5992 |
| DOI: | 10.2337/dc11-0472 |
| Popis: | OBJECTIVE The safety of dendritic cells to selectively suppress autoimmunity, especially in type 1 diabetes, has never been ascertained. We investigated the safety of autologous dendritic cells, stabilized into an immunosuppressive state, in established adult type 1 diabetic patients. RESEARCH DESIGN AND METHODS A randomized, double-blind, phase I study was conducted. A total of 10, otherwise generally healthy, insulin-requiring type 1 diabetic patients between 18 and 60 years of age, without any other known or suspected health conditions, received autologous dendritic cells, unmanipulated or engineered ex vivo toward an immunosuppressive state. Ten million cells were administered intradermally in the abdomen once every 2 weeks for a total of four administrations. The primary end point determined the proportion of patients with adverse events on the basis of the physician’s global assessment, hematology, biochemistry, and immune monitoring for a period of 12 months. RESULTS The dendritic cells were safely tolerated. There were no discernible adverse events in any patient throughout the study. Other than a significant increase in the frequency of peripheral B220+ CD11c− B cells, mainly seen in the recipients of engineered dendritic cells during the dendritic cell administration period, there were no statistically relevant differences in other immune populations or biochemical, hematological, and immune biomarkers compared with baseline. CONCLUSIONS Treatment with autologous dendritic cells, in a native state or directed ex vivo toward a tolerogenic immunosuppressive state, is safe and well tolerated. Dendritic cells upregulated the frequency of a potentially beneficial B220+ CD11c− B-cell population, at least in type 1 diabetes autoimmunity. |
| Databáze: | OpenAIRE |
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