Using Preclinical Models and Clinical Samples to Inform Mechanisms and Rational Combinations
Sergio A. Quezada Cancer Immunology Unit, University College London Cancer Institute, London, UK
My laboratory uses mouse models of cancer and clinical tumour samples to decipher the mechanisms governing the anti-tumour activity of immune modulatory antibodies in vivo. We and others have previously demonstrated that, in mice, anti-CTLA-4 monoclonal antibodies (mAbs) require Fc-gamma receptor (FcγR)-mediated depletion of CTLA-4hi tumour-infiltrating regulatory T (Treg) cells to promote tumour rejection. Despite high levels of CTLA-4 expression on Tregs infiltrating human cancers, the relevance of this mechanism in the human setting remains controversial. Using a mouse model expressing human FcγRs, and analysis of clinical samples from Ipilimumab-treated melanoma patients we investigate the potential contribution of Treg depletion to the activity of antibodies targeting human CTLA-4 and identify additional targets for antibodies with dual (checkpoint and Treg depleting) activities.
Credits: None available.
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