4-1BB (CD137) belongs to the TNFR superfamily and is expressed by activated CD4 helper T cells, B cells, natural killer cells, natural killer T cells, dendritic cells and Treg cells. 4-1BB is a potential therapeutic target as it enhances tumor rejection by upregulating T cells following activation and its engagement increases T cell proliferation and pro-inflammatory cytokine production. However, the liver toxicity associated with over immune activation has obstructed the clinical development of 4-1BB targeting therapies. To address the issue, Biocytogen has developed humanized B-h4-1BB mice as an efficient platform of both in vivo MOA and safety studies of 4-1BB antibody.