PD-L1-directed TLR7 Agonist PF-08046037

**Semantic type:** Pharmacologic Substance

**Definition:** An immune stimulating antibody conjugate (ISAC) consisting of a monoclonal antibody directed against the immunosuppressive ligand programmed cell death-1 ligand 1 (PD-L1; cluster of differentiation 274; CD274) conjugated, via a mannosidase-cleavable maleimidopropionyl-mannose (mp-mann) linker, to an imidazoquinoline-based Toll-like receptor (TLR) 7 agonist, with potential immunostimulatory and antineoplastic activities. Upon administration of PD-L1-directed TLR7 agonist PF-08046037, the anti-PD-L1 antibody targets and binds to PD-L1 expressed on tumor-associated antigen presenting cells (APCs) in the tumor microenvironment (TME). Upon binding, internalization and linker cleavage, the TLR7 agonist moiety is released, and binds to and activates TLR7. This stimulates APCs, including dendritic cells (DCs). The activation of DCs results in the production of proinflammatory cytokines, including interferon alpha (IFN-a), and the activation of cytotoxic T-lymphocytes (CTLs) and T-cell-mediated immune responses against tumor cells. The engineered Fc domain of the antibody moiety of PF-08046037 decreases Fc gamma receptor (FcgR) binding, which may prevent off-target immune activation. TLR7 is a member of the TLR family, which plays a fundamental role in pathogen recognition and activation of innate immunity. PD-L1, a transmembrane protein, is expressed on the surface of APCs and on many cancer cell types. PD-L1 binding to PD-1, a negative regulator of the immune system on activated T-cells, limits the expansion and survival of CD8-positive T-cells, suppresses the immune system and results in immune evasion.

**Synonyms:** - Anti-PD-L1 Monoclonal Antibody-TLR7 Agonist Conjugate PF-08046037 - ISAC PF-08046037 - Immune Stimulating Antibody Conjugate PF-08046037 - PF 08046037 - PF-08046037 - PF08046037 - SGN PDL1iT - SGN-PDL1iT - SGNPDL1iT