Immunostimulatory
monoclonal antibodies (mAbs) exert
antineoplastic effects by eliciting a novel or reinstating a pre-existing antitumor immune response. Most often, immunostimulatory mAbs activate T lymphocytes or natural killer (NK) cells by inhibiting immunosuppressive receptors, such as cytotoxic T lymphocyte-associated
protein 4 (CTLA4) or programmed cell death 1 (PDCD1, best known as PD-1), or by engaging co-stimulatory receptors, like CD40,
tumor necrosis factor receptor superfamily, member 4 (TNFRSF4, best known as OX40) or TNFRSF18 (best known as GITR). The CTLA4-targeting mAb
ipilimumab has been approved by the US Food and Drug Administration for use in patients with unresectable or metastatic
melanoma in 2011. The therapeutic profile of
ipilimumab other CTLA4-blocking mAbs, such as
tremelimumab, is currently being assessed in subjects affected by a large panel of solid
neoplasms. In the last few years, promising clinical results have also been obtained with
nivolumab, a PD-1-targeting mAb formerly known as
BMS-936558. Accordingly, the safety and efficacy of
nivolumab and other PD-1-blocking molecules are being actively investigated. Finally, various clinical trials are underway to test the therapeutic potential of OX40- and GITR-activating mAbs. Here, we summarize recent findings on the therapeutic profile of immunostimulatory mAbs and discuss clinical trials that have been launched in the last 14 months to assess the therapeutic profile of these immunotherapeutic agents.