The Activation of Natural Killer Cell Effector Functions by Cetuximab-Coated, Epidermal Growth Factor Receptor–Positive Tumor Cells is Enhanced By Cytokines

摘要: Purpose: Natural killer (NK) cells express an activating Fc receptor (FcγRIIIa) that mediates antibody-dependent cellular cytotoxicity (ADCC) and production of immune modulatory cytokines in response to antibody-coated targets. Cetuximab is a therapeutic monoclonal antibody directed against the HER1 antigen. We hypothesized NK cell cetuximab-coated tumor could be enhanced by administration cell–stimulatory cytokines. Experimental Design: Human stimulated with interleukin-2 (IL-2), IL-12, or IL-21 were assessed for ADCC secretion IFN-γ T cell–recruiting chemokines. cetuximab given nude mice bearing HER1-positive xenografts. Results: Stimulation human IL-2, resulted 3-fold 10-fold higher than was observed either agent alone. cell–derived significantly monocyte cells. Costimulated also secreted elevated levels chemokines (IL-8, macrophage inflammatory protein-1α, RANTES) direct migration naive activated treated cetuximab. The combination cetuximab, trastuzumab (an anti-HER2 antibody), mediated greater cytokine any Furthermore, effects murine model. Conclusions: These results show cetuximab-mediated activity can presence factors, therefore, may effective adjuvants administer, patients malignancies.