Abstract
Objective This study aims to examine the therapeutic potential of combined treatment with B cell targeted STALs and T cell targeted PLGA-R nanoparticles in treating K/BxN mice that develop spontaneous autoimmune arthritis to the self-antigen glucose-6-phosphate-isomerase (GPI).
Methods Siglec-engaging tolerance-inducing antigenic liposomes (STALs) that display both an antigen (Ag) and glycan ligands of the inhibitory co-receptor CD22 (CD22L) were prepared by thin film hydration method. Rapamycin encapsulated PLGA nanoparticles (PLGA-R) were prepared by the oil in water single emulsion method. The K/BxN arthritis mice were treated intravenously with GPI-STALs and PLGA-R nanoparticles prophylactically and therapeutically. Disease progression was monitored by paw thickness measurements and GPI-specific IgG titers were determined by serum ELISAs. Changes in cartilage and synovium were evaluated by histological analysis.
Results Co-administration of STALs together with PLGA-R to naïve mice induced more robust tolerance to multiple antigen challenges than either nanoparticle alone. Repeated dosing was beneficial as co-administration of 5 doses of GPI-STALs and PLGA-R prophylactically delayed disease onset until 11 weeks, and in some cases indefinitely. Therapeutic treatment of K/BxN mice with GPI-STALs and PLGA-R after disease symptoms are apparent showed prevention and, in some cases, even reversal of disease. In addition, histological examination of treated K/BxN mice showed normal cartilage and synovium and the absence of infiltrating immune cells into the joint space as compared to untreated mice.
Conclusion Together these data show synergy between B cell-tolerizing STALs and T cell-tolerizing PLGA-R and the potential to induce tolerance in early stage autoimmune disease.
Competing Interest Statement
The authors have declared no competing interest.