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), the first ribonuclease being evaluated as a therapeutic in humans, has progressed to phase III clinical trials in patients with unresectable 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 anti-cancer therapeutics.
Krauss
Jürgen
J
Natinal center for tumor diseases (NCT), Universit6y of Heidelberg, Im Neuenheimer Fild 350, D-69120 Heidleberg, Germany. juergen.krauss@med.uni-heidelberg.de
Arndt
Michaela A E
MA
Dübel
Stefan
S
Rybak
Susanna M
SM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D018796:Immunoconjugates / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D015202:Protein Engineering; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D012259:Ribonuclease, Pancreatic / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D018796:Immunoconjugates; D011993:Recombinant Fusion Proteins; D012259:Ribonuclease, Pancreatic