Development and characterization of a novel human CD137 agonistic antibody with anti-tumor activity and a good safety profile in non-human primates.

CD137 (4-1BB, TNFRSF9), an inducible T-cell costimulatory receptor, is expressed on activated T cells, activated NK cells, Treg cells, and several innate immune cells, including DCs, monocytes, neutrophils, mast cells, and eosinophils. In animal models and clinical trials, anti-CD137 agonistic monoclonal antibodies have shown anti-tumor potential, but balancing the efficacy and toxicity of anti-CD137 agonistic monoclonal antibodies is a considerable hindrance for clinical applications. Here, we describe a novel fully human CD137 agonistic antibody (PE0116) generated from immunized harbor H2L2 human transgenic mice. PE0116 is a ligand blocker, which is also the case for Utomilumab (one of the leading CD137 agonistic drugs); PE0116 partially overlaps with Urelumab's recognized epitope. In vitro, PE0116 activates NF-κB signaling, significantly promotes T-cell proliferation, and increases cytokine secretion in the presence of cross-linking. Importantly, PE0116 possesses robust anti-tumor activity in the MC38 tumor model. In vivo, PE0116 exhibits a good safety profile and has typical pharmacokinetic characteristics of an IgG antibody in preclinical studies of non-human primates. In summary, PE0116 is a promising anti-CD137 antibody with a good safety profile in preclinical studies.