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ADEPT and related concepts

K D Bagshawe1

  • 1Charing Cross and Westminister Medical School, London, UK.

Cell Biophysics
|January 1, 1994
PubMed
Summary

Antibody-directed enzyme prodrug therapy (ADEPT) enhances tumor selectivity. Strategies like plasma enzyme inactivation (PENCIL) and intravascular active drug inactivation (IVIAD) improve drug targeting and reduce toxicity.

Area of Science:

  • Biomedical Engineering
  • Pharmacology
  • Oncology

Background:

  • Antibody-based therapies offer improved selectivity but face limitations as delivery systems.
  • Restricting therapeutic action to tumor sites necessitates advanced strategies.
  • The Antibody-Directed Enzyme Prodrug Therapy (ADEPT) concept utilizes enzyme-prodrug pairs for enhanced selectivity.

Purpose of the Study:

  • To explore methods for augmenting the selectivity of antibody-enzyme conjugates (AECs) in drug delivery.
  • To address limitations of AECs, such as non-specific enzyme activity and drug leakage.
  • To propose novel strategies for improving the tumor-specific activation of prodrugs.

Main Methods:

  • Investigating the Antibody-Directed Enzyme Prodrug Therapy (ADEPT) concept.

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  • Evaluating strategies for controlling enzyme activity in plasma, such as PENCIL (plasma enzyme inactivation).
  • Proposing intravascular active drug inactivation (IVIAD) using enzyme-substrate interactions.

    • Main Results:

    • AEC selectivity is not inherently superior to antibodies alone; total catalytic activity depends on concentration and volume.
    • Controlling plasma enzyme activity is crucial to prevent premature prodrug activation.
    • IVIAD offers an alternative to PENCIL for managing active drug levels and reducing toxicity.

    Conclusions:

    • ADEPT requires secondary manipulation to achieve optimal tumor selectivity.
    • Strategies like PENCIL and IVIAD are essential for refining enzyme-prodrug systems.
    • Further development of these approaches can enhance the efficacy and safety of antibody-based cancer therapies.