CD137抗体

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     Black line: Control Antigen (100 ng);Purple line: Antigen (10ng); Blue line: Antigen (50 ng); Red line:Antigen (100 ng)    

  
  

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     Flow cytometric analysis of Ramos cells using CD137 mouse mAb (green) and negative control (red).    

  
  

CD137 (4-1BB), a member of the tumor necrosis factor receptor (TNFR) superfamily, is a co-stimulatory immune checkpoint molecule primarily expressed on activated T cells, natural killer (NK) cells, and dendritic cells. Its activation via binding to CD137 ligand (CD137L) triggers downstream signaling pathways (e.g., NF-κB), enhancing T-cell proliferation, survival, and effector functions while inhibiting apoptosis. This mechanism positions CD137 as a promising target for cancer immunotherapy, particularly in overcoming T-cell exhaustion in the tumor microenvironment.

Agonistic CD137 antibodies, designed to mimic ligand-induced activation, emerged as a strategy to amplify antitumor immunity. Preclinical studies demonstrated potent tumor regression in murine models, sparking clinical interest. Early trials, however, revealed dose-limiting toxicities, including hepatotoxicity, linked to excessive immune activation. For example, urelumab (anti-CD137 mAb) showed efficacy in melanoma and lymphoma but faced safety challenges, while utomilumab, a weaker agonist, exhibited better tolerability but modest clinical activity. These findings underscored the delicate balance between immune stimulation and systemic toxicity.

Current research focuses on optimizing CD137 targeting through bispecific antibodies, combination therapies (e.g., with PD-1/PD-L1 inhibitors), and localized delivery to minimize off-target effects. CD137 antibodies also hold potential in infectious disease and vaccine adjuvants. Despite challenges, their ability to reinvigorate antitumor immunity continues to drive innovation in next-generation immunotherapies.