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

Figure 2

Enavatuzumab showed diverse antitumor activities on different xenograft tumors. (a) Enavatuzumab or two variants of enavatuzumab containing mutations in the Fc region were incubated with mouse splenocytes. Binding to CD11b^high cells was measured by FACS. ADCC activities of enavatuzumab and its Fc mutant variants were evaluated by Cr-51 release with H520-TweakR cells as targets and mouse splenocytes as effectors at a ratio of 1 : 40. (b) Established SN12C tumors were treated with enavatuzumab, a variant of enavatuzumab with no FcγR binding, or a control antibody (10 mg/kg) three times a week for a total of seven doses, with dosing days indicated by the arrows above the graph. Dosing groups contained 10 animals each. Treatment with enavatuzumab, but not the Fc mutant, resulted in significant tumor growth inhibition on days 24–36 (). A375 tumors were similarly administered with nine doses of enavatuzumab, an Fc mutant variant, or a control antibody. Dosing groups contained 8 animals each, and significant growth inhibition was observed with both enavatuzumab and the Fc mutant on days 21–37 (). HCT116 and DLD-1 xenograft tumors were treated with enavatuzumab or a control antibody for nine or six doses ( or 10). Enavatuzumab treatment resulted in no tumor growth inhibition in either models.

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