ANTIBODY-DIRECTED ENZYME PRODRUG THERAPY (ADEPT) - Fusion Protein Technologies for Biopharmaceuticals: Applications and Challenges - page 350

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explored in clinical studies.

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23.6 CONCLUSIONS AND FUTURE OUTLOOK

ADEPT has shown feasibility as a treatment for cancer and
opportunities for developing it for diverse tumors and
targets with many different enzyme and prodrug systems.
It has the potential to be a most selective form of therapy
but a number of critical points need to be addressed some
ofwhichtendtobeignored.
A successful ADEPT system requires the following:

Sustained high concentrations of the enzyme in tumors
Elimination of enzyme from blood and other normal
tissue (may require enzyme inactivation/clearance
step) without affecting enzyme concentration in the
tumor
Nontoxic prodrug
Highly toxic drug with short half-life and nonrepair-
able tumor cell DNA damage
Nonimmunogenic system components for repeated
treatments to enhance efficacy.

These goals are achievable and we are currently devel-
oping an enhanced ADEPT for cancer, utilizing the original
idea of a three-phase system [17].

ACKNOWLEDGMENTS

I am grateful to Professor KD Bagshawe for helpful advice
and critical comments.

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