TolDC Therapy Development Service

Tolerogenic dendritic cell (tolDC) therapy involves manipulating dendritic cells through engineering to make the cells more tolerant to specific antigens and lead the immune system remain unoverreactive to self-tissue or foreign antigens. Our company provides advanced research services and materials to speed up your development of tolDC cells therapies with high efficacy for Autoimmune Diseases & Inflammation.

TolDC Therapy in Autoimmune Diseases & Inflammation

Dendritic cells (DCs) are the most potent antigen-presenting cells necessary for the activation and differentiation of naive T cells, thus initiating the process of immunogenesis. In turn, DCs play crucial role in regulating the equilibrium state of immune system by immune tolerance, as it is clear that DCs deficiency is positively correlated with the incidence of autoimmune diseases. In response to various stimuli, such as cytokines, small molecule drugs, etc., DCs acquire tolerance functions by different mechanisms to suppress immune responses.

• Contact-Dependent Clonal Anergy
  After T cells recognize the antigens presented by tolDCs, co-inhibitory molecular signals are transmitted from tolDCs to T cells through cell-cell contact and inhibit the proliferation of T cells.
• Metabolites and Cytokines Modulating T Cells
  The production of cytokines, including IL-10, IL-27 and TGF-β, as well metabolites, such as lactate and retinoic acid, limits the activity of effector and memory T cells promote the differentiation of regulatory T cells, which in turn secret TGF-β and IL-10, forming a tolerogenic loop.
• Clonal Deletion
  The Fas-L of tolDCs binds to the Fas of T cells to induce apoptosis, which also coincides with programmed cell death triggered by binding of TRAIL produced by tolDCs to TRAILR of T cells.

Fig.1 Summary of DC-targeted therapies in systemic lupus erythematosus (SLE) (Kaewraemruaen C., et al., 2020)

The multi-mechanism feature of DCs has prompted a large number of attempts to use tolDCs in animal models of various autoimmune diseases. TolDCs eliminate inflammation in autoimmune diseases without interfering with protective immunity, so as to achieve the purpose of re-settle the immune system.

For instance, tolDCs targeting the CD40 and CD80 have been shown to significantly arrest the onset of diabetes in the Type 1 Diabetes experimental models. Moreover, the tolDCs collected from patients with rheumatoid arthritis produce less costimulatory molecules and pro-inflammatory cytokines, resulting in a reduced ability to activate antigen-specific T cells. Taken together, the potential of tolDCs to suppress immune responses in autoimmune environment promotes the belief that tolDC therapy could soon be used in clinical practice.

Our Services

TolDC therapy holds the potential to provide a more targeted and safer alternative to conventional immunosuppressive therapeutics for Autoimmune Diseases & Inflammation. Our company provides leading-edge development service for TolDC therapy as the following workflow:

In addition to different methods to generate tolDCs, we provide the tolDCs modification services including but not limited to:

Our Advantages

Supported by experienced senior researchers in cellular immunology and cell engineering, and equipped with a comprehensive platform for cell therapy development, our company is dedicated to providing considerate services to facilitate the development of therapeutic tolDCs for Autoimmune Diseases & Inflammation. Please contact us for more detailed information and our team will get back to you promptly.

Reference

1. Kaewraemruaen, Chamraj et al. "Dendritic cells as key players in systemic lupus erythematosus." Asian Pacific journal of allergy and immunology 38,4 (2020): 225-232.