Journal
IMMUNOTHERAPY
Volume 3, Issue 2, Pages 193-211Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/IMT.10.90
Keywords
ADEPT; antibody-directed enzyme prodrug therapy; antibody-enzyme fusion protein; cancer; immunogenicity; immunoRNase
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Funding
- Clement Wheeler-Bennett Memorial Trust
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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.
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