Intracellular route and mechanism of action of ERB-hRNase, a human anti-ErbB2 anticancer immunoagent

Human anti-ErbB2 immunoRNase with Erbicin fused to HP-RNase (ERB-hRNase) is a fully human immunoRNase made up of human pancreatic RNase fused to a human antiErbB2 scFv. It binds selectively with high affinity to ErbB2positive cells, and specifically inhibits their proliferation, in vitro and in vivo. An investigation of its mechanism of action and its intracellular destination has revealed that ERB-hRNase depends on its RNase activity for cytotoxic action; it reaches the cytosol directly from the endosomal compartment; it Is inhibited by the cytosolic RNase inhibitor (cRI), but the levels that ERB-hRNase reaches in the cytosol neutralize cRI, thus inducing cell death by apoptosis. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.