Melton / Knox Enzyme-Prodrug Strategies for Cancer Therapy

Erscheinungsjahr 2012
ISBN: 978-1-4615-4823-2
Verlag: Springer US
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 257 Seiten, eBook

Antibody-directed enzyme prodrug therapy (ADEPT) directly addresses the major problem in cancer chemotherapy-its lack of selectivity. Antibody delivery combined with the amplification provided by the enzymatic activation of prodrugs enables selection to be made between tumour and normal tissue. ADEPT offers a novel field of opportunities in the therapy of systemic cancer and may be a major advance for the treatment of solid tumours. This book is the first to describe ADEPT in detail. Each chapter reviews an aspect of the immunology, enzymology, biochemistry, chemistry, and cancer chemotherapy which have been integrated into the ADEPT concept. An additional chapter describes the related approach of gene-directed enzyme prodrug therapy (GDEPT). This latter approach is still in its infancy but ADEPT has entered the clinic. The initial clinical studies with ADEPT are included and discussed in detail.

Zielgruppe

Research

Autoren/Hrsg.

Melton, Roger G.

Knox, Richard J.

Inhaltsverzeichnis

1 Introduction.- 1. Introduction.- References.- 2 Prodrugs in Cancer Chemotherapy.- 1. Introduction.- 2. Uses of Prodrugs in Cancer Chemotherapy.- 3. Clinical Use of Prodrugs.- References.- 3 Factors Influencing Tumor-Selective Localization of Antibody Conjugates.- 1. Introduction.- 2. Tumor Physiology.- 3. Properties of the Monoclonal Antibody Vector.- 4. Tumor Antigens.- 5. Manipulation of Tumor Antigenic Expression.- 6. Evaluation of Antigenic Targets for ADEPT.- 7.In VitroCell Culture Problems.- 8. Unforeseen Problems of Specificity.- References.- 4 Enzymes and Prodrugs Used for ADEPT.- 1. Introduction.- 2. Enzymes and Prodrugs Used for ADEPT.- 3. Conclusions.- References.- 5 The Design and Synthesis of Prodrugs for Antibody-Directed Enzyme Prodrug Therapy (ADEPT).- 1. Introduction.- 2. Prodrugs Used in ADEPT.- 3. Summary.- References.- 6 Preparation and Purification of Antibody-Enzyme Conjugates for Therapeutic Applications.- 1. Introduction.- 2. Production of Antibody Fragments.- 3. Chemical Coupling of Antibodies to Enzymes.- 4. Alternatives to Chemical Coupling.- 5. Purification of Conjugates.- 6. Postpurification Modifications.- 7. Future Developments.- References.- 7 Phage Technology for Producing Antibody-Enzyme Fusion Proteins.- 1. Introduction.- 2. Antibody-Targeted Cancer Therapy.- 3. Potential of Engineered Antibodies for Therapy.- 4. Single-chain Fv Antibodies.- 5. The Phage System.- 6. Target Antigens.- 7. Engineered Antibody-Enzyme Fusion Proteins in ADEPT.- 8. Practical Considerations.- 9. Conclusions.- References.- 8 Early Clinical Studies with ADEPT.- 1. Introduction.- 2. Initial Clinical Studies.- 3. Second Clinical Study.- 4. Conclusions.- References.- 9 Gene-Directed Enzyme Prodrug Therapy (GDEPT) of Cancer.- 1. Introduction.- 2. Why GDEPT?.- 3.Enzymes and Prodrugs Used for GDEPT.- 4. Conclusions.- References.- Enzymes and Prodrugs Proposed for Cancer Therapy.- References.