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Updated: Jun 4, 2026

Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody
Published on: May 16, 2020
Antibody-enzyme fusion proteins for cancer therapy
Carima Andrady1, Surinder K Sharma, Kerry A Chester
1Cancer Research UK Targeting & Imaging Group, Department of Oncology, UCL Cancer Institute, Paul O'Gorman Building, University College London, 72 Huntley Street, London WC1E6BT, UK. c.andrady@ucl.ac.uk
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.
Insights
Genetically engineered antibody-enzyme fusion proteins offer novel cancer therapy strategies. These proteins target tumors either by activating prodrugs or by directly delivering toxic enzymes to cancer cells.
Area of Science:
- Biomolecular technology
- Cancer therapy
- Immunotherapy
Background:
- Genetically fused antibody-enzymes represent a significant advancement in biomolecular technology.
- These fusion proteins have emerged as promising tools for targeted cancer treatment.
Purpose of the Study:
- To review two distinct strategies employing antibody-enzyme fusion proteins for cancer therapy.
- To discuss the progression of these strategies from conceptualization to clinical trials.
Main Methods:
- Antibody-directed enzyme prodrug therapy (ADEPT): Pretargeting tumors with antibody-enzymes, followed by administration of an inactive prodrug.
- Direct enzyme-based therapy: Utilizing antibody-enzyme fusions to deliver cytotoxic enzymes directly into tumor cells for internalization and cell death induction.
Main Results:
- ADEPT system converts inactive prodrugs into active therapeutic agents at the tumor site.
- Direct enzyme delivery system leverages antibody internalization to trigger tumor cell death, notably with ribonucleases.
Conclusions:
- Antibody-enzyme fusion proteins offer versatile platforms for targeted cancer treatment.
- Both prodrug activation and direct enzyme delivery strategies show potential in preclinical and clinical settings.
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