anti-PD-1/TGFbRII fusion protein LBL-015

A tetravalent bispecific fusion protein targeting both the human negative immunoregulatory checkpoint receptor programmed cell death protein 1 (PD-1; PDCD1; CD279) and human transforming growth factor beta (TGF-beta; TGFb), with potential immune checkpoint modulating and antineoplastic activities. Upon administration, anti-PD-1/TGF-beta receptor II (TGFbRII) fusion protein LBL-015 targets and binds to PD-1 and TGF-beta and prevents the activation of PD-1 and TGF-beta-mediated signaling pathways in the tumor microenvironment (TME). This abrogates the PD-1- and TGFb-mediated immunosuppression in the TME, increases natural killer (NK) cell and cytotoxic T-lymphocyte (CTL) activities, and inhibits tumor cell proliferation in susceptible tumor cells. PD-1, an inhibitory receptor belonging to the immunoglobulin superfamily (IgSF), is expressed on activated T lymphocytes; it functions as an immune checkpoint that negatively regulates T-cell activation and effector function when activated by its ligands and plays an important role in tumor evasion from host immunity. TGF-beta, a pro-inflammatory mediator, is upregulated in certain types of cancers and is involved in cancer cell proliferation, tumor progression, migration and invasion, and the suppression of the immune response.