Stimulation of natural killer cells with a CD137-specific antibody enhances trastuzumab efficacy in xenotransplant models of breast cancer

NK cells and cancer: you can teach innate cells new tricks

“…CD137 (also known as 4-1BB and TNFRSF9) is expressed on both cytotoxic T cells and activated NK cells, and agonist mono clonal antibodies augment antitumour activity in mouse models 122 , although there are conflicting data on the role of CD137 in NK cell activation 123 . Agonist CD137 antibodies enhance the human NK cell-mediated killing of breast tumours 124 and B cell lymphomas 125 induced by trastuzumab and rituximab, respectively. Although agonist CD137 antibodies showed significant toxicities when used at high doses in the early clinical trials 126 , lower doses might serve to increase antitumour efficacy when combined with other checkpoint blockade therapeutics or with tumour-specific antibodies that induce ADCC.…”

Identification of CD245 as myosin 18A, a receptor for surfactant A: A novel pathway for activating human NK lymphocytes

“…Stimulation of the CD137 (4-1BB) receptor present on NK cells has been shown to increase the efficacy of cetuximab, trastuzumab and rituximab in both in vitro and in vivo models of human cancer. [9][10][11] The use of monoclonal antibodies that modulate the expression of CD137 at the NK cell surface, such as DY12 mAb (Fig. 5), could be interesting in such application.…”

“…8 Consequently, the engagement of CD137 increases cetuximab-, rituximab-, and trastuzumab-dependent NK cell cytotoxic function in different cancer models. [9][10][11] NK cell activation is dominantly suppressed if the inhibitory NKR bind to MHC class I molecules on target cells. 2 In humans, these receptors mainly belong to C-type lectin receptors, as the NKG2A heterodimer, or to the KIRs family.…”

Preclinical and clinical evaluation of elotuzumab, a SLAMF7-targeted humanized monoclonal antibody in development for multiple myeloma

“…In addition, as proteasome inhibition stimulates apoptosis, reduces angiogenesis, cytokine signaling and cell adhesion, and can increase the susceptibility of multiple myeloma cells to NK cell-mediated killing [54,55], combination with bortezomib may also be effective [56,57]. In preclinical studies, overnight pretreatment of multiple myeloma cells with antibodies enhanced the efficacy of the ADCC-mediating mAb trastuzumab [62]. In addition, immunostimulation with an agonistic CD137 antibody in mouse models of myeloma has been shown to activate NK cells [61].…”