Second generation CD2-targeting LFA-3 fusion protein SBT115301 to restore immune homeostasis in autoimmune disease.

In autoimmunity, an imbalance of effector (T(eff)) and regulatory (T(reg))T cells contributes to inflammation and tissue destruction. CD2, highly expressed on T(eff) and at lower levels on T(reg) and naive T cells (T(n)), is an attractive target for depleting T(eff) at sites of inflammation. SBT115301 is a second generation CD2-targeting fusion protein containing the cognate receptor of CD2, lymphocyte function associated antigen-3 (LFA-3; CD58). In in vitro and in vivo studies, SBT115301 preferentially decreased CD2(hi)-expressing T(eff) cells compared to T(reg) and T(n). In a phase 1 clinical trial, SBT115301 selectively reduced memory T cells. SBT115301 was well tolerated aside from decreases of CD4(+) T cells in some participants in the highest dose IM and IV cohorts. Anti-drug antibodies decreased exposure of SBT115301 in some participants without affecting the pharmacodynamics. These data support further study of SBT115301 as a monotherapy or in combination with other drugs in autoimmune indications.