Selective targeting of auto reactive B cells using bispecific molecules

Abstract Type 1 diabetes occurs when autoreactive T cells attack insulin-producing in pancreatic islets. B promote disease by acting as essential antigen presenting cells. Targeted immune therapy for treatment and prevention of autoimmune diseases is preferable to drugs that cause global immunosuppression. We therefore investigated the efficacy three constructs designed specifically target neutralize anti-insulin Construct one has a 4-arm PEG backbone with insulin attached 2 arms (insulin-PEG). two trisaccharide molecule acts ligand inhibitory receptor CD22 on remaining (insulin-PEG-CD22L). consists directly conjugated CD22L (insulin-CD22L). In vitro experiments using transgenic demonstrate insulin-PEG unexpectedly promotes excessive proliferation upregulation CD86 anti-CD40 treated Addition (insulin-PEG-CD22L) restores cell responses baseline but no overall benefit. Conversely, insulin-CD22L blunts effects stimulation, reducing 15% IgM surface expression 50% . alone effect stimulated Preliminary vivo data 2-photon imaging shows binds spleen, lymph nodes islets within 30 minutes injection. Thus, this novel construct directs dampening T1D, making it promising therapeutic intervention may also be useful paired anti-T treatments. P20GM1133117 T32GM008545 5T32AI7163-43