Bispecific epitope binding protein comprising anti-4-1bb antibody and a pd-1 protein or fragments thereof and use thereof

Abstract

The present invention provides a bispecific epitope binding protein comprising an anti-4-1BB agonist antibody and a PD-1 protein or a fragment thereof that binds to PD-L1 with high affinity. The bispecific epitope binding protein simultaneously and independently binds to 4-1BB and PD-L1, which engage 4-1BB upregulated T cells, especially effector CD8+ T cells, with tumor cells expressing PD-L1. These interactions induce strong activation of the cytotoxic activity of anti-tumor effector CD8+ T cells by both blocking PD-1/PD-L1-mediated inhibitory signaling and activating 4-1BB-mediated costimulatory signaling in mouse models. This bispecific epitope binding protein has a much stronger oncolytic effect compared to each component alone.