Engineering Dimeric EGFR-directed IgA Antibodies Reveals a Central Role of CD147 during Neutrophil-mediated Tumor Cell Killing of Head and Neck Squamous Cancer Cells

• DOI: 10.4049/jimmunol.2300544
• Publication Date: 2024-05-24T13:26:34Z
• Authors: Anabel Zwick; Felix Leon Braun; Lennert Jochen Weber; Manuel Linder; Maximilian Linxwe...; Stefan Lohse
• Keywords: 0303 health sciences; 03 medical and health sciences

Human IgA Abs engage neutrophils for cancer immunotherapy more effectively than IgG Abs. Previous studies demonstrated that engineering approaches improved biochemical and functional properties. In this study, we report a novel, to our knowledge, IgA2 Ab against the epidermal growth factor receptor generated by protein polymerization. The resulting molecule covalent linkage of L H chains an effective polymerization joining chain. engineered dimer outperformed its monomeric variant in experiments on Fab-mediated modes action binding Fc receptor. capacity Ab-dependent cell-mediated cytotoxicity (ADCC) adherent growing target cells was cell line dependent. Although displayed long-term efficacy vulva carcinoma A431, there notable in-efficacy human papillomavirus (HPV)- head neck squamous (HNSCC) lines. However, highly triggered neutrophil-mediated HPV+ HNSCC Short-term ADCC correlated with cells' expression ability cell-conditioned media enhance CD147 surface level neutrophils. Notably, lines significant increment releasing soluble reduced induction membranous compared HPV- cells. may impair proper IgA-Fc binding, enhanced IgA-neutrophil-mediated dose-dependent manner. Thus, impedance-based assays provided valuable information regarding target-effector interaction identified as putative critical parameter cytotoxicity.