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Development and characterization of a novel human CD137 agonistic antibody with anti‐tumor activity and a good safety profile in non‐human primates.
- Source :
- FEBS Open Bio; Dec2022, Vol. 12 Issue 12, p2166-2178, 13p
- Publication Year :
- 2022
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 22115463
- Volume :
- 12
- Issue :
- 12
- Database :
- Complementary Index
- Journal :
- FEBS Open Bio
- Publication Type :
- Academic Journal
- Accession number :
- 160529533
- Full Text :
- https://doi.org/10.1002/2211-5463.13494