A Novel Fully Human Antitumor ImmunoRNase Targeting ErbB2-Positive Tumors

Abstract

A second generation anti-ErbB2 ImmunoRNase, called Erb-hcAb-RNase, was obtained by the fusion of Erb-hcAb, a human compact anti-ErbB2 antibody, with human pancreatic ribonuclease (HP-RNase or RNase 1). We show herein that Erb-hcAb-RNase retains the enzymatic activity of human pancreatic RNase and specifically binds to ErbB2-positive cells with an affinity comparable to that of the parental Erb-hcAb. Moreover, this novel immunoRNase is endowed with an effective and selective antiproliferative action for ErbB2-positive tumor cells both in vitro and in vivo. Its antitumor activity is more potent than that of the parental Erb-hcAb as the novel immunoconjugate has acquired RNase-based cytotoxicity in addition to the inhibitory growth effects, antibody-dependent and complement-dependent cytotoxicity of the compact antibody. Erb-hcAb-RNase could be a promising candidate for the immunotherapy of ErbB2-positive tumours as it combines the advantages of the first generation scFv-based immunoRNase with those of a fully functional antibody