Definition

A monoclonal antibody directed against the transforming growth factor beta (TGFbeta) activator glycoprotein A repetitions predominant (GARP; leucine-rich repeat-containing protein 32; LRRC32), with potential immunomodulating and antineoplastic activities. Upon administration, anti-GARP monoclonal antibody HLX60 selectively targets and binds to GARP. This specifically blocks the GARP-mediated release of the cytokine transforming growth factor-beta 1 (TGF-b1), thereby relieving the immunosuppression caused by TGF-b1, reversing the immunosuppressive nature in the tumor microenvironment (TME), and improving anti-tumor immune responses. In addition, HLX60 induces antibody dependent cell-mediated cytotoxicity (ADCC), which leads to a depletion of GARP-positive tumor cells and immunosuppressive regulatory T cells (Tregs). The depletion of Tregs further leads to a reversal of immunosuppression mediated by GARP-positive Tregs and enhances the immune response to tumor cells. GARP, a transmembrane protein highly expressed on activated, immunosuppressive Tregs in the TME, is essential for the expression of TGF-b1 on the cell surface of activated Tregs; it plays an important role in regulation of the immune cell function and the immunosuppressive nature of Tregs.