Humoral immunity responses against EGFR-positive tumor cells induced by xenogeneic EGFR expressed in the yeast Pichia pastoris

Abstract

The breaking of immune tolerance against self epidermal growth factor receptor (EGFR) should be a promising approach for the treatment of those receptor-positive tumors. We have previously shown that human EGFR as a xenoantigen induced a specific antitumor activity against EGFR-positive mouse tumors. Our further studies demonstrated that a recombinant form of extracellular domain of mouse EGFR provoked active cellular immunity responses against EGFR-positive human tumors. In this study, we investigated whether the recombinant murine EGFR expressed in the yeast Pichia pastoris would induce humoral immunity responses against EGFR-positive human tumors. To test this concept, polyclonal immunoglobulin (IgG), which was produced by vaccinating the rabbits with the recombinant mEGFR, was purified from the sera of the rabbits. We evaluated the antitumor activity of the polyclonal IgG in the nude mice bearing A431 tumors. Mice were i.v. treated with the purified IgG at 100 mg/kg 1 day before the mice were inoculated with the tumor cells and then twice per week for 4 weeks. Our results showed that the polyclonal IgG would efficiently inhibit the growth of the solid tumor in vivo. The antitumor effect of the polyclonal IgG may result from the increasing rate of apoptosis and induction of differentiation of the tumor cells in vivo. The present findings may provide insight into treatment of EGFR-positive tumors through induction of the humoral immunity responses based on xenogeneic homologous EGFR.