Anti-(epidermal growth factor) receptor monoclonal antibodies for the induction of antibody-dependent cell-mediated cytotoxicity against squamous cell carcinoma lines of the head and neck.

摘要: Squamous cell carcinomas of the head and neck (SCCHN) frequently display high levels epidermal growth factor receptor (EGFR). Since EGFR is expressed on surface it may form a suitable target for anticancer therapy with anti-receptor monoclonal antibodies (mAb). Besides interference receptor/ligand interactions, binding mAb to leads immunoglobulin-coated tumour cells that induce or enhance non-specific immune effector mechanisms like antibody-dependent cell-mediated cytotoxicity (ADCC). In established lines SCCHN (UM-SCC 11B, 14C, 22B, 8029 NA) we investigated antitumour activity allogeneic peripheral blood mononuclear (PBMC) in combination rat (ICR 62), mouse (EMD 55900), humanized 72000) anti-EGFR mAb. addition, autologous PBMC were available line UD-SCC 4. The protein content ranged between 170 fmol/mg 8100 protein, MCF-7 served as receptor-negative controls. against targets was determined 96-well microtitre-plate monolayer cultures by colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay after coincubation 4 h, 24 h 72 at ratios 1:1, 5:1, 10:1 20:1. subpopulations obtained macrophage depletion (plastic adherence) natural killer (NK) enrichment (magnetic bead negative selection). Prolonged time exposure increased effector:target revealed marked alone. This destruction enhanced considerably rat, but not Increased partly correlated an intensification ADCC accompanied decreased primary cytotoxicity. utilization suggested mainly NK-cell-mediated ADCC, which appeared benefit directly indirectly, e.g. via secretion cytokines, from other components. conclusion, 62) able generate strong monolayers SCCHN.