Targeted therapeutic RNases (ImmunoRNases)

Abstract

Immunotoxins combining antibody specificity with bacterial or plant toxins are limited by their strong immunogenicity and non-specific toxicity. Ribonucleases of the RNase A protein superfamily provide a solution to address these issues because they show potent antineoplastic activity on cell internalization but do not show appreciable immunogenicity or non-specific toxicity. Their therapeutic value is demonstrated by RNase derived from the frog (Rana pipiens), Onconase^® (ONC, Alfacell, Inc., New Jersey, USA), the first and only RNase being evaluated in clinical trials at present. Conjugation or fusion of RNases to tumor specific antibodies is a promising approach to further boost tumor cell killing of these compounds. This review focuses on ‘targeted RNases/ImmunoRNases’ as promising novel anticancer therapeutics.

Keywords::

• angiogenin
• antibody therapy
• CD22⁺ lymphoma
• CD30⁺ lymphoma
• human pancreatic RNase
• ImmunoRNase
• immunotherapy
• immunotoxins
• Onconase
• ranpirnase
• ribonucleases
• RNase A family
• RNases
• targeted RNase
• tumor therapy

Acknowledgement

The authors acknowledge the financial support from the German Federal Ministry for Education and Research (BMBF) through the German National Genome Research Network 2 (NGFN2, Grant No. 01GR0428). We also thank M Hust for reading the manuscript.

Notes