Abstract Description CD19 CAR T-effector (CAR19Teff) therapy is promising in autoimmunity but limited by the inability to modulate pathogenic T cells and safety concerns like cytokine release syndrome and neurotoxicity. To address these limitations, we developed CD19 CAR engineered regulatory T cells (CAR19 EngTregs), which offer B cell depletion with the crucial capacity to suppress pathogenic T cells via bystander suppression and lower inflammatory cytokine secretion. We engineered human CAR19 EngTregs with stab…

<p dir="ltr">Genome-wide association studies have identified <i>SH2B3 </i>as an important non-MHC gene for islet autoimmunity and type 1 diabetes (T1D). In this study, we found a single <i>SH2B3</i> haplotype significantly associated with increased risk for human T1D. Fine mapping has demonstrated the most credible causative variant is the single nucleotide rs3184504*T polymorphism in <i>SH2B3</i><i>.</i> To better characterize the role of SH2B3 in T1D, we used…

<p dir="ltr">Genome-wide association studies have identified <i>SH2B3 </i>as an important non-MHC gene for islet autoimmunity and type 1 diabetes (T1D). In this study, we found a single <i>SH2B3</i> haplotype significantly associated with increased risk for human T1D. Fine mapping has demonstrated the most credible causative variant is the single nucleotide rs3184504*T polymorphism in <i>SH2B3</i><i>.</i> To better characterize the role of SH2B3 in T1D, we used…

Tregs have the potential to establish long-term immune tolerance in patients recently diagnosed with type 1 diabetes (T1D) by preserving β cell function. Adoptive transfer of autologous thymic Tregs, although safe, exhibited limited efficacy in previous T1D clinical trials, likely reflecting a lack of tissue specificity, limited IL-2 signaling support, and in vivo plasticity of Tregs. Here, we report a cell engineering strategy using bulk CD4+ T cells to generate a Treg cell therapy (GNTI-122) that stably expresse…

Abstract Genome-wide association studies have identified SH2B3 as an important non-MHC gene for islet autoimmunity and type 1 diabetes (T1D). In this study, we found a single SH2B3 haplotype significantly associated with increased risk for human T1D, and this haplotype carries the single nucleotide variant rs3184504*T in SH2B3. To better characterize the role of SH2B3 in T1D, we used mouse modeling and found a T cell-intrinsic role for SH2B3 regulating peripheral tolerance. SH2B3 deficiency had minimal effect on T…