CD137 Costimulatory Receptor Agonists

CD137 Costimulatory Receptor Agonists – Target Pipeline List 07/2019

Targets: CD137; 4-1BB; TNFRSF9; Tumor Necrosis Factor Receptor SuperFamily member 9

This Target Pipeline List provides an overview of selective and bispecific CD137 receptor agonists in development for treatment of solid tumors.

CD137 (4-1BB/TNFRSF9) is a transmembrane costimulatory T-cell receptor belonging to the TNF receptor superfamily. CD137 on T and NK cells enhances adaptive immune responses and is a critical mediator of antitumor immunity. CD137 signaling requires receptor clustering normally facilitated by the trimeric CD137 ligand (CD137L). Alternatively, CD137 signaling can be triggered either directly by agonistic monoclonal antibodies (mAbs) or indirectly via crosslinking of CD137 binding mAbs by Fcγ receptors on neighboring cells. The development of CD137 targeted agents for cancer therapy has been hampered by on-target off-tumor toxicity in the case of agonist, monospecific, bivalent mAbs or limited antitumor activity in the case of crosslinking mAbs.

• New developments of CD137-targeted molecules include
• Novel Selective CD137 Agonists;
• Bispecific Bispecific CD137 x Tumor Associated Antigen-Targeted Molecules;
• Bispecific CD137 x PD-L1 Antibodies;
• Other Bispecific CD137 Targeted Molecules.

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