Enavatuzumab, a Humanized Anti-TWEAK Receptor Monoclonal Antibody, Exerts Antitumor Activity through Attracting and Activating Innate Immune Effector Cells

Figure 1

Enavatuzumab induces effector cell activation and tumor cell killing in vitro. (a) Human PBMCs were coincubated with Cr-51-labeled tumor target cells with E : T at 40 : 1 for 4 hr in the presence of enavatuzumab. Tumor cell cytotoxicity was calculated based on Cr-51 released into culture supernatant. Antibody-independent cell cytotoxicity (AICC) was also calculated. Experiments were performed with PBMCs from 4 donors. Representative data collected from one donor are shown. (b) Human PBMCs, cultured either alone or with indicated tumor cells at a 10 : 1 ratio, were treated with enavatuzumab or a control antibody. 24 hrs later, CD54 and CD16 levels were assessed on both monocytes (Mono) and NK cells by flow cytometry. Experiments were performed with PBMCs from 8 donors. Representative data collected from one donor were shown. (c) PBMCs were cultured with SN12C cells at the indicated ratios for 24 hr in the presence of enavatuzumab or a control antibody, after which CD69 was assessed on NK cells by flow cytometry (left) or cytokeratin18 levels were quantified in cell supernatants as a measure of tumor cell cytotoxicity (right). Enavatuzumab treatment increased CD69 levels at all E : T ratios tested (representative data from 4 donors) but significantly stimulated cytotoxicity only at 10 : 1 and 25 : 1 ratios (, ).

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