Challenges in tolerogenic dendritic cell therapy for autoimmune diseases: the route of administration

Abstract

Tolerogenic dendritic cells (tolDCs) are a promising strategy to treat autoimmune diseases since they have the potential to re-educate and modulate pathological immune responses in an antigen-specific manner and, therefore, have minimal adverse effects on the immune system compared to conventional immunosuppressive treatments. TolDCs therapy has demonstrated safety and efficacy in different experimental models of autoimmune disease, such as multiple sclerosis (MS), type 1 diabetes (T1D) and rheumatoid arthritis (RA). Moreover, data from phase I clinical trials have shown that therapy with tolDCs is safe and well tolerated by MS, T1D and RA patients. Nevertheless, various parameters need to be optimized to increase tolDCs efficacy. In this regard, one important parameter to be determined is the most appropriate route of administration. Several delivery routes, such as intravenous, subcutaneous, intraperitoneal, intradermal, intranodal and intra-articular routes, have been used in experimental models as well as in phase I clinical trials. This review summarizes data obtained from preclinical and clinical studies of tolDCs therapy in the treatment of MS, T1D and RA and their animal models, as well as data from the context of cancer immunotherapy using mature peptide-loaded DC, and data from in vivo cell tracking experiments, to define the most appropriate route of tolDCs administration in relation to the most feasible, safest, and effective therapeutic use.

Mechanism of Action of Oral Salmonella-Based Vaccine to Prevent and Reverse Type 1 Diabetes in NOD Mice

“…In addition, tol-DCs eliminated autoreactive CD8 + T-cells, caused clonal deletion and anergy, and converted peripheral T-cells subsets into regulatory T-cells [ 111 ]. In the present study, tol-DCs exhibited an immature DC phenotype, low MHC class II, induction of Tregs, expression of PD-L1 and PD1, alterations in chemokine receptors, decreased pro-inflammatory cytokine secretion, and enhanced immunoregulatory cytokine secretion [ 111 , 112 , 113 , 114 ].…”

Autoantigen‐Dexamethasone Conjugate‐Loaded Liposomes Halt Arthritis Development in Mice

“…The antigen chosen in this study was hPG since it is used to induce arthritis in the mouse model, however, in human patients, we would likely require a different antigen, such as (citrullinated) peptides derived from fibrinogen, vimentin and collagen, or heat shock protein (HSP)70. [ 65 ] The only clinical trial carried out so far with a similar treatment strategy for rheumatoid arthritis showed that the liposomes were well‐tolerated and induced T cells with tolerogenic TCR signaling and exhaustion profiles. [ 66 ]…”

Helios as a Potential Biomarker in Systemic Lupus Erythematosus and New Therapies Based on Immunosuppressive Cells

“…This concentration of therapeutic cells at specific targets could avoid the side effects derived from systemic and non-specific dissemination of DCs in the bloodstream. In this context, different approaches are being tested: (1) direct inoculation of DCs into the LNs [ 161 ]; (2) induction of enhanced CCR7 expression, a fundamental chemotaxis receptor on DCs [ 162 ]; and (3) the magnetic targeting of DCs coupled to iron oxide nanoparticles (IONPs) [ 163 ]. This latter strategy will be addressed below as a promising nanotechnology approach to biological problems.…”