IL-10 secreting Dendritic Cells to re-establish Antigen-Specific Tolerance in T-cell Mediated Diseases”
Where : CNR conference room
Host: Dr. Carmen Gianfrani
Contact Phone : 081/6132224
Silvia Gregori, PhD
San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy
will present:
IL-10 secreting Dendritic Cells to re-establish Antigen-Specific Tolerance in T-cell Mediated Diseases”
The prominent role of dendritic cells (DC) in promoting T-cell tolerance and the development of methods to generate clinical grade products allowed the clinical application of tolerogenic DC-based therapies for the control of unwanted immune responses. We focused our research on IL-10-secreting DC recently identified as the best-suited cells for DC-based therapies. We identified and characterized DC-10, an inducible subset of human DC endowed with the ability of spontaneously and upon activation releasing high levels of IL-10, and of inducing T regulatory Type 1 (Tr1) cells. Although, concluded clinical trials demonstrated the safety and feasibility of DC-based therapies approach, the stability of the infused DC products and the maintenance of their tolerogenic properties in vivo remain open issues to be tackled for improving the safety and the efficacy of DC-based cell therapies. Our hypothesis is that infusion of DC genetically modified by newly developed tolerogenic lentiviral vectors (LV) encoding autoAg-derived epitopes (LV-DC) will promote the in vivo generation of Ag-specific tolerance via down-regulation of autoAg-specific pathogenic T cell responses and induction of long-living autoAg-specific Tregs. To this aim we developed LV-platforms that allow the expression of specific autoAg epitope and pro-tolerogenic molecules. Our preliminary data show that LV-DC can modulate T cell responses both in vitro and in vivo and that infusion of LV-DC dampens Ag-specific T cell responses in vivo. The success of our strategies will help designing a safer DC-based cell therapy, abrogating the boosting of autoimmunity, and to stably preserve the tolerogenic properties of in vivo transferred DC.