Antibody–Enzyme Fusion Proteins for Cancer Therapy

Abstract

Advances in biomolecular technology have allowed the development of genetically fused antibody–enzymes. Antibody–enzyme fusion proteins have been used to target tumors for cancer therapy in two ways. In one system, an antibody–enzyme is pretargeted to the tumor followed by administration of an inactive prodrug that is converted to its active form by the pretargeted enzyme. This system has been described as antibody-directed enzyme prodrug therapy. The other system uses antibody–enzyme fusion proteins as direct therapeutics, where the enzyme is toxic in its own right. The key feature in this approach is that the antibody is used to internalize the toxic enzyme into the tumor cell, which activates cell-death processes. This antibody–enzyme system has been largely applied to deliver ribonucleases. This article addresses these two antibody–enzyme targeting strategies for cancer therapy from concept to (pre)clinical trials.

KEYWORDS::

• ADEPT
• antibody-directed enzyme prodrug therapy
• antibody–enzyme fusion protein
• cancer
• immunogenicity
• immunoRNase

Acknowledgements

The authors are indebted to Professor Kenneth Bagshawe for his helpful comments and criticisms.

Financial & competing interests disclosure

Carima Andrady is generously supported by a Clement Wheeler-Bennett Memorial Trust PhD studentship. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

Carima Andrady is generously supported by a Clement Wheeler-Bennett Memorial Trust PhD studentship. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.