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Antibody-Directed Enzyme Prodrug Therapy (ADEPT) for Cancer

  • Surinder K. Sharma
  • Kenneth D. Bagshawe
Chapter
Part of the Macromolecular Anticancer Therapeutics book series (CDD&D)

Abstract

Antibody-directed enzyme prodrug therapy (ADEPT) is a system that aims to restrict the action of a high concentration of a cytotoxic drug to cancer sites. This is achieved by using an antibody (or antibody fragment) to deliver a non-human enzyme to cancer sites.

To avoid systemic toxicity, enzyme levels in blood must be very low at the time of prodrug administration. The rapid clearance of enzyme from blood may be achieved by either using a glycosylated fusion molecule or by addition of a second component that inactivates the enzyme before a non-toxic prodrug that is a substrate for the enzyme is given. The low molecular weight drug thus generated diffuses through the tumour mass but has a short half-life so that it does not reach normal cell renewal systems. Many pre-clinical studies using a variety of enzymes and prodrugs confirmed efficacy of this approach but only one system has progressed to clinical trials. These clinical studies identified new challenges that need to be addressed when developing new ADEPT systems.

Keywords

Bacterial Enzyme Nitrogen Mustard Cytosine Deaminase Enzyme Conjugate Catalytic Antibody 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

ADEPT

Antibody-directed enzyme prodrug therapy

AEC

Antibody–enzyme conjugate

CEA

Carcinoembryonic antigen

CMDA

4-[(2-chloroethyl)(2-mesyloxyethyl) amino] benzoyl-l-glutamic acid

CMDA

Benzoic acid mustard prodrug

CPG2

(Carboxypeptidase G2)

CPT-11

Irinotecan

DMSO

Dimethyl sulphonic acid

18F FDG-PET

18fluorine-labelled fluoro-deoxy glucose -positron emission tomography

5-Fu

5-fluorouracil

hCE-2

human carboxylesterase

hCG

human chorionic gonadotropin

MFE

An anti-CEA scFv antibody

MFECP

A recombinant fusion protein consisting of the anti-CEA scFv antibody MFE fused with enzyme carboxypeptidase G2

MTD

Maximal tolerable dose

SB43gal

SB43 galactosylated

Tag 72

Tumour-associated glycoprotein 72 antigen

Notes

Acknowledgments

We thank Professor Richard Begent for the critical review of this manuscript and Cancer Research UK for grant support.

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.CR UK Targeting & Imaging Group, Res Department of OncologyUCL Cancer InstituteLondonUK
  2. 2.Department of Medical OncologyImperial College LondonLondonUK

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