1. Schematic representation of mechanisms leading to the synergy of anti-CD137 and anti–PD-1 immunostimulatory mAbs.
Schematic representation of mechanisms leading to the synergy of anti-CD137 and anti–PD-1 immunostimulatory mAbs. Conceivably, the same tumor-reactive T cells are released from the inhibitory influence of PD-1 on CD28 and T-cell receptor (TCR) signaling while receiving active costimulation via CD137 to keep them alive and fitter to perform their antitumor function. Pharmacodynamic interactions occur between both mAb-targeted molecules as for example: (i) PD-1 blockade and CD28 signaling lead to increased expression of CD137 and (ii) CD137-enhanced INFγ production would lead to more intense PD-L1 expression in the tumor microenvironment. As depicted, targeted forms of CD137 agonists to the tumor microenvironment have been designed, including bispecific antibodies and other biomolecule formats. These smarter, local CD137 agonists will be safer and more potent. Such agents are also to be combined with PD-1 blockade. APC, antigen-presenting cell.
Elisabeth Pérez-Ruiz et al. Clin Cancer Res 2017;23:
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