GARP:TGF-β1 complex

Class

Anti-GARP:TGF-β1 monoclonal antibody (ABBV-151)

Pathway

blocks activation/release of latent TGF-β1 presented by GARP on regulatory T cells and other cells, relieving TGF-β-mediated immunosuppression; combined with anti-PD-1 budigalimab

GARP (glycoprotein A repetitions predominant) is a cell-surface protein expressed prominently on regulatory T cells, platelets, and some stromal cells. It anchors an inactive, or latent, form of the signaling protein TGF-β1 at the cell surface. When released and activated, TGF-β1 restrains immune responses, helping maintain tolerance to self but also allowing tumors to escape immune surveillance. The GARP:TGF-β1 complex is a checkpoint for how and where this latent growth factor gets converted to its active, signaling-competent form. An antibody that binds this complex can block activation or release of TGF-β1 specifically from GARP-expressing cells, rather than neutralizing TGF-β1 broadly throughout the body. This targeted approach is intended to relieve TGF-β-driven immunosuppression within the tumor microenvironment while sparing TGF-β's other physiological roles. Because regulatory T cells within tumors are a major source of this GARP-bound TGF-β1, disrupting the complex is expected to reduce local immune suppression and support the activity of T cells directed against cancer cells. This mechanism is being explored in combination with antibodies blocking PD-1, a distinct immune checkpoint, on the premise that simultaneously addressing two independent suppressive pathways produces a more complete restoration of anti-tumor immune activity than either approach alone.