Drug Targeting

1. Front Matter

   Pages i-x

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2. Strategies

   1. Chemical Construction of Immunotoxins

      • Victor Ghetie, Ellen S. Vitetta

      Pages 1-26

   2. Construction of Ribonuclease–Antibody Conjugates for Selective Cytotoxicity

      • Dianne L. Newton, Susanna M. Rybak

      Pages 27-35

   3. Intracellular Targeting Using Bispecific Antibodies

      • Vic Raso

      Pages 37-50

   4. Antibody Conjugation Methods for Active Targeting of Liposomes

      • Steven M. Ansell, Troy O. Harasym, Paul G. Tardi, Susan S. Buchkowsky, Marcel B. Bally, Pieter R. Cullis

      Pages 51-68

   5. Folate as a Targeting Device for Proteins Utilizing Folate Receptor-Mediated Endocytosis

      • Robert J. Lee, Philip S. Low

      Pages 69-76

   6. Preparation of Recombinant RNase Single-Chain Antibody Fusion Proteins

      • Dianne L. Newton, Susanna M. Rybak

      Pages 77-95

3. Theoretical Aspects

   1. Practical Considerations in the Exploitation of Passive Tumor Targeting

      • Gillian D. Thomas

      Pages 97-113

   2. Effect of Dose, Molecular Size, and Binding Affinity on Uptake of Antibodies

      • Gillian D. Thomas

      Pages 115-132

   3. Inhibition of Tumor Blood Flow

      • Lai-Ming Ching, Wilson William R., Baguley Bruce C.

      Pages 133-157

4. Applications

   1. 10 Targeting in Myocardial Infarction

      • Ban An. Khaw, Vladimir P. Torchilin

      Pages 159-191

   2. 11 Targeting HIV-Infected Cells

      • Seth H. Pincus

      Pages 193-214

   3. 12 Making Fusion Toxins to Target Leukemia and Lymphoma

      • Robert J. Kreitman, Ira Pastan

      Pages 215-226

   4. Antibody-Bearing Liposomes as Chloroquine Vehicles in Treatment of Murine Malaria

      • Ajay K. Agrawal, Chhitar M. Gupta

      Pages 227-239

   5. 14 Immunotargeting of Catalase to the Pulmonary Vascular Endothelium

      • Vladimir R. Muzykantov

      Pages 241-254

   6. 15 Targeted Gene Transfer

      • Ellen K. Wasan, Dorothy L. Reimer, Pierrot Harvie, Spencer Kong, Frances M. P. Wong, Marcel B. Bally

      Pages 255-304

5. Back Matter

   Pages 305-318

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Advances in understanding the molecular mechanisms of disease together with the advent of recombinant DNA and other technologies have opened opportunities for a vast array of novel therapeutic biopharmaceuticals and diagnostic agents. However, even natural biomolecules present a myriad of problems that limit their potential as pharmaceutical agents. Rapid degra- tion and elimination, immunological reactions, and toxicity are often asso- ated with new biopharmaceuticals, much as with conventional agents. Targeted delivery systems have the potential to increase the efficacy of existing diagnostic and therapeutic agents and also create an opportunity for the use of new pharmaceuticals, substances that themselves can be harmful to normal tissues. Both passive and active targeting have been exploited. Most active targ- ing strategies have focused on antibody conjugates since preparation of highly specific monoclonal antibodies is well established. However, a new wave of c- jugates exploiting other ligands is underway. Access to the target tissue remains an obstacle and is an area where passive targeting can be useful. In Drug Targeting: Strategies, Principles, and Applications we have tried to compile a state-of-the-art volume on current targeting approaches. The first section focuses on certain key strategies applied to date, and how to build the antibody– ligand constructs. This is followed by a section on theoretical considerations for t- geting, focusing on approaches relevant to solid tumors. The last section deals with some experimental and clinical applications of targeted drug delivery systems.

• PolyMASC Pharmaceuticals, London, UK

  G. E. Francis

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