BDCA2 (CLEC4C) / TACI

Class

Bispecific fusion protein (anti-BDCA2 antibody fused to TACI-derived domain; Fc-engineered for enhanced ADCC and extended half-life)

Pathway

Dual inhibition of plasmacytoid dendritic cell (BDCA2) and B-cell (TACI/BAFF-APRIL) autoimmune signaling

This mechanism combines two distinct autoimmune-relevant targets in a single bispecific fusion protein: BDCA2 (also called CLEC4C), a receptor found only on plasmacytoid dendritic cells (pDCs), and TACI, a receptor on B cells that binds the survival factors BAFF and APRIL. pDCs are the body's principal source of type I interferon, a signaling protein that drives inflammation in diseases such as lupus and related autoimmune conditions. Engaging BDCA2 suppresses interferon production and can mark pDCs for elimination. The TACI-derived portion of the molecule acts as a decoy receptor, capturing BAFF and APRIL before they can reach B cells, thereby reducing B-cell survival, antibody production, and the generation of harmful autoantibodies. Combining these two arms in one molecule allows simultaneous dampening of the innate immune signal (interferon from pDCs) and the adaptive immune signal (autoantibody-producing B cells), two pathways that reinforce each other in systemic autoimmune disease. The Fc portion of the antibody has been modified to enhance antibody-dependent cellular cytotoxicity, a process by which immune cells destroy antibody-tagged target cells, and to extend the molecule's circulating half-life. This dual-pathway design is intended to address disease drivers that a single-target agent might only partially control.