Generation, Characteristics and Clinical Trials of Ex Vivo Generated Tolerogenic Dendritic Cells

Yonsei Med J. 2018 Sep;59(7):807-815. doi: 10.3349/ymj.2018.59.7.807.


Dendritic cells (DCs) play a key role not only in the initiation of primary immune responses, but also in the development and maintenance of immune tolerance. Numerous protocols have been developed to generate tolerogenic DCs (tolDCs) ex vivo, and the therapeutic efficacy of ex vivo-generated tolDCs has been demonstrated in autoimmune disease animal models. Based on successes in small animal models, several clinical trials have been completed or are on-going in patients with autoimmune diseases such as rheumatoid arthritis, type 1 diabetes, multiple sclerosis, and Crohn's disease. Here we describe the methods used to generate tolDCs ex vivo, and the common features shared by tolDCs. In addition, we overview five completed clinical trials with reported outcomes and summarize the tolDC-based clinical trials that are currently registered with the U.S. National Institutes of Health. Although the number of tolDC-based clinical trials is much smaller than the hundreds of clinical trials using immunogenic DCs, tolDC-based treatment of autoimmune diseases is becoming a reality, and could serve as an innovative cellular therapy in the future.

Keywords: Dendritic cell; autoimmune disease; cellular therapy; clinical trial; immune tolerance.

Publication types

  • Review

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / therapy
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / therapy*
  • Cell Culture Techniques
  • Clinical Trials as Topic*
  • Crohn Disease / immunology
  • Crohn Disease / therapy
  • Dendritic Cells / immunology*
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / therapy
  • Humans
  • Ichthyosiform Erythroderma, Congenital / immunology
  • Ichthyosiform Erythroderma, Congenital / therapy
  • Immune Tolerance*
  • Lipid Metabolism, Inborn Errors / immunology
  • Lipid Metabolism, Inborn Errors / therapy
  • Muscular Diseases / immunology
  • Muscular Diseases / therapy

Supplementary concepts

  • Chanarin-Dorfman Syndrome