4-1BB-mediated cancer immunotherapy: ‘mission impossible’ for non-engineered IgGs?

Increasing tumor-specific immune responses with immunostimulatory monoclonal antibodies (mAbs) is a promising strategy in cancer therapy. Antagonistic mAbs blocking signaling through inhibitory receptors such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death-1 (PD-1) have been shown to induce sustained anti-tumor responses in many cancers across various histologies, and agonistic mAbs targeting activator receptors are undergoing clinical trials (1).