CD137 is a member of the tumor necrosis factor (TNF) receptor family. Its alternative names are tumor necrosis factor receptor superfamily member 9 (TNFRSF9), 4-1BB and induced by lymphocyte activation (ILA). It is of interest to immunologists as a co-stimulatory immune checkpoint molecule.
CD137 can be expressed by activated T cells, but to a larger extent on CD8 than on CD4 T cells.
The best characterized activity of CD137 is its costimulatory activity for activated T cells. Crosslinking of CD137 enhances T cell proliferation, IL-2 secretion, survival and cytolytic activity. Further, it can enhance immune activity to eliminate tumors in mice.
Upon administration, anti-CD137 agonistic antibody LVGN6051 binds to and activates CD137 expressed on a variety of leukocyte subsets including activated T lymphocytes and natural killer (NK) cells. This enhances CD137-mediated signaling, induces cytokine production and promotes T-cell mediated anti-tumor immune responses.
For more scientific rationale, please visit CD137/4-1BB and xLinkAbTM.
We are conducting Phase I trials of LVGN6051 alone or in combination with anti-PD-1 antibody in the USA (NCT04130542), in adult patients with advanced malignancies. No MTD was reached at 7 mg/kg monotherapy and 4 mg/kg q3w monotherapy was determined as RP2D. Preliminary antitumor activity in late stage cancer patients was observed. Combination with pembrolizumab induced rapid antitumor responses in advanced cancer patients with immune-cold tumor or relapsed from prior immunotherapies. We've got the approval of IND in China in 2020, and the bridging testing is on-going.