Autologous Dendritic Cell Therapy for Type 1 Diabetes Suppression: A Safety Study

Summary

The proposed studies describe a randomized trial to evaluate the safety of a new diabetes-suppressive cell vaccine, consisting of autologous monocyte-derived dendritic cells treated ex vivo with antisense phosphorothioate-modified oligonucleotides targeting the primary transcripts of the CD40, CD80 and CD86 co-stimulatory molecules (immunoregulatory DC; iDC). The hypothesis to be tested in this study is that iDC are safe and without toxicity in established type 1 diabetic patients. Fifteen (15) individuals exhibiting fully-established, insulin-dependent type 1 diabetics, without any diabetes-related complications, infectious disease, or other medical anomaly, will be enrolled to establish safety of the approach. 7/15 volunteers will be administered autologous control dendritic cells and 8/15 will be administered iDC. The study is anticipated to be complete by twelve (12) months. Currently, other than a humanized anti-CD3 antibody with considerable side effects, there is no other means to reverse new-onset type 1 diabetes. These studies will be the first ever to employ autologous dendritic cell transfer to suppress an autoimmune disease and to perhaps reverse it early on in the clinical process.

Timeline

Start

2007-03

Primary completion

2012-01

Completion

2016-02

Publications

• Results Harnaha J, Machen J, Wright M, Lakomy R, Styche A, Trucco M, Makaroun S, Giannoukakis N. Interleukin-7 is a survival factor for CD4+ CD25+ T-cells and is expressed by diabetes-suppressive dendritic cells. Diabetes. 2006 Jan;55(1):158-70.
• Results Machen J, Harnaha J, Lakomy R, Styche A, Trucco M, Giannoukakis N. Antisense oligonucleotides down-regulating costimulation confer diabetes-preventive properties to nonobese diabetic mouse dendritic cells. J Immunol. 2004 Oct 1;173(7):4331-41. doi: 10.4049/jimmunol.173.7.4331.
• Phillips BE, Garciafigueroa Y, Engman C, Trucco M, Giannoukakis N. Tolerogenic Dendritic Cells and T-Regulatory Cells at the Clinical Trials Crossroad for the Treatment of Autoimmune Disease; Emphasis on Type 1 Diabetes Therapy. Front Immunol. 2019 Feb 6;10:148. doi: 10.3389/fimmu.2019.00148. eCollection 2019.

Drugs

Indications