engineered toxin body targeting PD-L1 MT-6402

An engineered toxin body (ETB) composed of a single chain variable fragment (scFv) targeting the immunosuppressive ligand programmed cell death-1 ligand 1 (PD-L1; cluster of differentiation 274; CD274), fused to the enzymatically active de-immunized, ribosome-inactivating cytotoxic payload Shiga-like toxin-A subunit (SLTA) and a class I antigen derived from the human cytomegalovirus (CMV) phosphoprotein pp65, with potential immunomodulatory and antineoplastic activities. Upon administration, the scFv moiety of ETB targeting PD-L1 MT-6402 specifically targets and binds to PD-L1-expressing tumor and immune cells in the tumor microenvironment (TME). Upon internalization, the SLTA moiety is released and acts as an N-glycosidase, which binds to and cleaves an adenine nucleobase in the 28S RNA component of the 60S subunit of ribosomes and prevents ribosome activity. This inhibits protein synthesis and leads to apoptosis in PD-L1-expressing tumor and immune cells in the TME. In addition, MT-6402 delivers the foreign class I antigen derived from CMV pp65 peptide. This may result in a CMV-specific immune response against PD-L1-expressing tumor and immune cells in the TME. PD-L1, a transmembrane protein, is expressed on the surface of certain immune cells 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.