The Pharmacology of Monoclonal Antibodies

1. Front Matter

   Pages I-XXI

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2. Human Monoclonal Antibodies

   1. Front Matter

      Pages 1-1

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   2. Human Monoclonal Antibody Technology

      • K. James

      Pages 3-22

   3. Recombinant Therapeutic Human Monoclonal Antibodies

      • J. W. Larrick, R. Balint

      Pages 23-48

   4. Transgenic Approaches to Human Monoclonal Antibodies

      • N. Lonberg

      Pages 49-101

3. Genetically Engineered Monoclonal Antibodies

   1. Front Matter

      Pages 103-103

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   2. Humanization of Monoclonal Antibodies

      • G. E. Mark, E. A. Padlan

      Pages 105-134

   3. Applications for Escherichia coli-Derived Humanized Fab’ Fragments: Efficient Construction of Bispecific Antibodies

      • P. Carter, M. L. Rodrigues, M. R. Shalaby

      Pages 135-145

4. MAb Conjugates and Fusions

   1. Front Matter

      Pages 147-147

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   2. Immunotoxins

      • S. H. Pincus

      Pages 149-178

   3. Antibody-Enzyme Fusion Proteins and Bispecific Antibodies

      • E. Haber

      Pages 179-197

   4. Three Generations of Recombinant CD4 Molecules as Anti-HIV Reagents

      • A. Traunecker, K. Karjalainen

      Pages 199-206

5. Combinatorial Libraries

   1. Front Matter

      Pages 207-207

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   2. Chemical and Biological Approaches to Catalytic Antibodies

      • K. D. Janda, Chen Y.-C. Jack

      Pages 209-241

   3. The Combinatorial Approach to Human Antibodies

      • C. F. Barbas III

      Pages 243-266

6. Expression of MAbs/MAb Fragments

   1. Front Matter

      Pages 267-267

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   2. Antibodies from Escherichia coli

      • A. Plückthun

      Pages 269-315

   3. Structure, Function and Uses of Antibodies from Transgenic Plants and Animals

      • A. Hiatt, M. Hein

      Pages 317-330

   4. Some Aspects of Monoclonal Antibody Production

      • R. G. Rupp

      Pages 331-344

7. Medical Applications

   1. Front Matter

      Pages 345-345

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It has been almost 20 years since the discovery by Kohler and Milstein of the technology to produce monoclonal antibodies (MAbs), a discovery that promised revolutionary changes in research, clinical diagnosis and human therapy. From today's perspective, it is fair to conclude that this promise has been realized in two areas of the three. As research tools, MAbs have been invaluable: their ability to selectively bind and localize specific antigens, detect and identify new ligands and their receptors, and agonize and/or antagonize specific molecular interactions continues to provide a useful and enabling technology to basic research endeavors. Similarly, MAbs have demonstrated enormous practical impact as diagnostic tools. Recent advances in clinical diagnostic medicine continue to rely heavily on the use of MAb-based reagents for detecting and localizing antigens of clinical import. In contrast, however, MAbs have not proven to have major impact on human disease therapy. With the single exception of an immunosup­ pressive MAb against the T-cell antigen, CD3, MAbs have as yet found few meaningful applications as therapeutic agents. During the 1980s, a set of technologies to clone, modify and express genes encoding MAbs was developed. These breakthroughs permitted MAbs to be genetically engineered which consequently gave them the potential to greatly enhance their therapeutic utility as well as significantly expand their research and diagnostic applications. New MAbs, fragments of MAbs, bispecific MAbs, single-chain MAbs, and fusions of MAbs with other gene products became available for study.

• Combinatorial Cloning
• Klonung
• Monoclonal Antibodies
• Monoklonaler Antikörper
• Polymerase Chain Reaction

• Biopharmaceuticals Smith Kline Beecham Pharmaceuticals, King of Prussia, USA

  Martin Rosenberg

• Department of Molecular Genetics, Smith Kline Beecham Pharmaceuticals, King of Prussia, USA

  Gordon P. Moore

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