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Anti-tumor monoclonal antibodies eliminate tumor cells through different mechanisms including antibody-mediated cell cytotoxicity and generation of long-term anti-tumor T cell responses. In a recent publication, DiLillo and Ravetch demonstrate how this vaccinal effect is mediated by engagement of Fcγ receptors expressed on antigen-presenting cells. [ABSTRACT FROM AUTHOR]

Immunomodulatory antibodies influence the direction and magnitude of immune responses against cancer. Significant efficacy has been demonstrated across multiple solid tumour types within clinical trials. Recent preclinical studies indicate that successful outcome relies upon mechanistic activity extending beyond simple receptor stimulation or blockade. In addition to blocking co-inhibitory signals in secondary lymphoid organs, cytotoxic T-lymphocyte antigen (CTLA)-4 antibodies mediate depletion of tumour-infiltrating regulatory T cells by antibody-dependent cellular cytotoxicity (ADCC). This mechanism appears to be common to other immunomodulatory antibodies including those targeting OX40 and glucocorticoid-induced TNFR-related protein (GITR). If verified in the human setting, these findings have significant implications for antibody design, biomarker discovery, and the development of synergistic combinatorial therapies. [ABSTRACT FROM AUTHOR]