Cell-depleting agents assessment in preclinical models

Depletion of undesirable immune cells has shown to be a promising approach to treat cancer. B-cell-depleting antibodies such as rituximab are often used to treat patients with lymphoma and was shown to improve patients’ survival. Cell depletion can be triggered by antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP) and complement-dependent cytotoxicity (CDC). ADCP and ADCC activities are mediated by Fcγ receptors (FcγR) expressed on immune cells such as natural killer (NK) and macrophages. Translatable assessment of cell-depleting agents in preclinical models requires the presence of functional immune cells and expression of FcγR receptors. Importantly, FcγR expression in mouse and human are distinct, thus increasing the complexity of depleting antibodies assessment studies in preclinical models. Herein, we described two preclinical humanized models for assessment of cell-depleting agents.