Suppression of murine experimental autoimmune encephalomyelitis by interleukin-2 receptor targeted fusion toxin, DAB389IL-2

Previously we have shown that DAB389IL-2, a recombinant fusion toxin targeting IL-2R bearing cells, suppressed disease in the rat experimental autoimmune encephalomyelitis (EAE) model of acute multiple sclerosis (MS). Our present study demonstrates that DAB389IL-2 can also effectively suppress acute (A)-EAE, relapsing (R)-EAE and chronic (C)-EAE in mouse demyelinating models. DAB389IL-2 significantly suppressed mitogenic proliferation of spleen cells while mutant fusion proteins DAglu53B389IL-2 and DAB389IL-28–10 did not. EAE was successfully suppressed when DAB389IL-2 was administered in various regimens between days 1 and 15 post immunization in all three models. CD4+IL-2R+ cells were reduced in the spleen but not in the lymph nodes of DAB389IL-2-treated mice during A-EAE while the number of CD8+ cells was unchanged. DAB389IL-2 also significantly reduced the number of CD4+, CD8+, CD25+, TCRγδ+ phenotype and CD11b+ macrophages/microglia within spinal cord lesions. These data strongly suggest that DAB389IL-2 specifically targeted myelin protein-activated CD4+ T cells and strengthens the argument for the use of DAB389IL-2 in treatment strategies for MS.