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Antibody Directed Enzyme Prodrug Therapy (ADEPT): Trials and tribulations
Surinder K Sharma1, Kenneth D Bagshawe2
1Research Department of Oncology, UCL Cancer Institute, University College London, 72 Huntley Street, London WC1E 6BT, UK.
Abstract:
Antibody directed enzyme prodrug therapy has the potential to be an effective therapy for most common solid cancers. Clinical studies with CPG2 system have shown the feasibility of this approach. The key limitation has been immunogenicity of the enzyme. Technologies now exist to eliminate this problem. Non-immunogenic enzymes in combination with prodrugs that generate potent cytotoxic drugs can provide a powerful approach to cancer therapy. ADEPT has the potential to be non -toxic to normal tissue and can therefore be combined with other modalities including immunotherapy for greater clinical benefit.
Insights
Antibody Directed Enzyme Prodrug Therapy (ADEPT) shows promise for solid cancers. Overcoming enzyme immunogenicity with new technologies enhances its potential for targeted, less toxic cancer treatment.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- Antibody Directed Enzyme Prodrug Therapy (ADEPT) is a promising strategy for treating solid tumors.
- Clinical trials using the CPG2 system demonstrated the feasibility of ADEPT.
- A major challenge for ADEPT has been the immune response against the therapeutic enzyme.
Purpose of the Study:
- To explore the potential of Antibody Directed Enzyme Prodrug Therapy (ADEPT) for solid cancer treatment.
- To address the limitation of enzyme immunogenicity in ADEPT.
- To highlight the advantages of non-immunogenic enzymes in combination with potent cytotoxic prodrugs.
Main Methods:
- Utilizing advanced technologies to develop non-immunogenic enzymes.
- Combining these modified enzymes with prodrugs designed to release potent cytotoxic agents.
- Leveraging antibody targeting to direct the enzyme-prodrug system to tumor sites.
Main Results:
- Development of non-immunogenic enzymes effectively mitigates the immune response.
- The combination of non-immunogenic enzymes and specific prodrugs creates a potent anti-cancer effect.
- ADEPT demonstrates potential for reduced toxicity to normal tissues.
Conclusions:
- Eliminating enzyme immunogenicity significantly enhances ADEPT's therapeutic potential.
- Non-immunogenic ADEPT offers a powerful and potentially less toxic approach to cancer therapy.
- ADEPT can be integrated with other treatments, such as immunotherapy, for improved clinical outcomes.
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