Antibody-targeted RNase fusion proteins (ImmunoRNases) for cancer therapy

Ribonucleases (RNases) of the superfamily A exhibit potent antineoplastic activity yet do not mediate appreciable immunogenicity or non-specific toxicity in both animal models and cancer patients. Ranpirnase (Onconase (R)), the first ribonuclease being evaluated as a therapeutic in humans, has progressed to phase III clinical trials in patients with un-resectable mesothelioma. Conjugation of RNases to internalizing tumor-targeting monoclonal antibodies was shown to enhance specific cell killing by several orders of magnitude both in vitro and in animal models. In this review we describe the development and current status of genetically engineered 2(nd) generation immunoRNases as promising novel anticancer therapeutics.