Fig. 4: Zanidatamab mediates Fc effector functions including potent CDC, and ADCC and ADCP. | Nature Communications

Fig. 4: Zanidatamab mediates Fc effector functions including potent CDC, and ADCC and ADCP.

From: An anti-HER2 biparatopic antibody that induces unique HER2 clustering and complement-dependent cytotoxicity

Fig. 4: Zanidatamab mediates Fc effector functions including potent CDC, and ADCC and ADCP.

a Zanidatamab mediated CDC with normal human serum (NHS) in high HER2-expressing tumor cells (AU565, NCI-H2170, OE-19, NCI-N87, BT-474, SK-BR-3; HER2 3+); trastuzumab, pertuzumab, and tras + pert (1:1) are inactive. b Zanidatamab mediated the highest C1q and C3 fragment (C3b/iC3b/C3dg) deposition on NCI-N87 cells in the presence of NHS. Zanidatamab and tras + pert binding in presence of NHS resulted in enhanced C1q (left) C3b/iC3b/C3dg (right) deposition in NCI-N87 cells compared to trastuzumab, pertuzumab or negative control. Zanidatamab mediated concentration-dependent ADCC (c) and ADCP (d) in NCI-N87 cells with comparable activity to trastuzumab, pertuzumab and tras + pert. In a–d, data are mean ± SEM from n = 3 (AU565, NCI-H2170, OE-19, BT-474, SK-BR-3) or n = 6 (NCI-N87) independent experiments. In b–d data are mean ± SEM from n = 3 independent experiments. In c, d n = 3 independent experiments performed with biologically independent PBMC samples (c), or with macrophage derived from three biologically independent PBMC samples (d). Gating strategy for b, c and d is shown in Supplementary Fig. 12d, a, b, respectively. Source data are provided as a Source Data file.

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