Unleashing the Power of T Cells

Pieris Pharmaceuticals’ PRS-344/S095012 is a 4-1BB/PD-L1 bispecific being developed in collaboration with Servier. PRS-344 consists of a PD-L1-targeting antibody and 4-1BB-targeting Anticalin® proteins genetically fused to each arm of the antibody’s C-terminal heavy chain. 4-1BB is a co-stimulatory receptor belonging to the TNFR superfamily.

Clustering of 4-1BB on the surface of T cells leads to T cell activation, proliferation, and cytokine secretion. The mode of action of PRS-344 is to promote 4-1BB clustering by bridging 4-1BB-positive T cells with PD-L1-positive tumor cells, providing a potent co-stimulatory signal to tumor antigen-specific T cells. PRS-344 is intended to localize 4-1BB activation in the tumor in a PD-L1-dependent manner.

Preclinical data shows that the synergistic effect observed by simultaneously targeting PD-L1 and 4-1BB is stronger with PRS-344 than with the combination of anti-PD-L1 and anti-4-1BB antibodies.