InhaltsangabeSection I: Human Monoclonal Antibodies.- 1 Human Monoclonal Antibody Technology.- A. Introduction.- I. Why Produce Human Monoclonals?.- II. Chapter Aims.- III. Approach Used.- B. General Production Strategies.- I. Introduction.- II. Source of Immune Lymphocytes.- 1. Usual Sources.- 2. In Vitro Immunization.- 3. Generating Immune Lymphocytes in Severe Combined Immunodeficiency Mice.- III. Processing of Lymphoid Tissues.- IV. Immortalization Strategies.- 1. Introduction.- 2. Cell Fusion.- 3. Epstein-Barr Virus Fusion.- 4. Combined Epstein-Barr Virus Transformation and Cell Fusion.- 5. Novel Approaches.- V. Selection, Cloning and Expansion.- 1. Introduction.- 2. Selection.- 3. Cloning.- 4. Expansion.- 5. Additional Evaluation.- VI. Bispecific and Trispecific Antibodies.- C. Human Monoclonal Targets.- I. Antibody Specificities Generated.- II. Application of Human Monoclonal Antibody Technology.- 1. Introduction.- 2. Tumour Field.- 3. AIDS Research.- 4. Autoimmunity.- 5. Future Targets.- D. Limitations of Orthodox Technology.- I. Introduction.- II. Why Is Antibody Secretion Unsatisfactory?.- III. Is Unsatisfactory Secretion Related to Cell Surface Phenotype or Cytokine Secretion?.- E. Conclusion.- I. Impact and Potential of Recombinant Technology.- 1. Chimeric and Humanized Antibodies.- 2. Repertoire Cloning.- 3. Combining Cell and Gene Cloning Technologies.- References.- 2 Recombinant Therapeutic Human Monoclonal Antibodies.- A. Therapeutic Human Monoclonal Antibodies.- B. Rapid Direct Cloning of Antibody Variable Regions.- C. Genetically Engineered Chimeric Monoclonal Antibodies.- I. Chimeric Antibodies.- 1. Summary of Work with Therapeutic Chimeric Monoclonal Antibodies.- II. Recombinant Conjugates and Fusion Proteins.- 1. Immunotoxins.- 2. A Recombinant Monoclonal Antibody Linked to Tissue-Type Plasminogen Activator.- 3. T Cell Receptor Conjugates.- 4. Growth Factor Conjugates.- 5. Other Fusion Proteins.- 6. Antibody-Enzyme Conjugates for Cancer.- D. Reshaped or Composite Antibodies.- E. Immortalization of the Immunoglobulin Repertoire Using rDNA Technology.- F. Recombinatorial Antibody Libraries.- G. Phage Antibody Libraries: Wholly Synthetic Monoclonal Antibodies.- References.- 3 Transgenic Approaches to Human Monoclonal Antibodies.- A. Introduction.- B. Competing Technologies for the Generation of Therapeutic Antibodies.- C. Origins of Antibody Diversity.- I. Functional Requirements for a Human Immunoglobulin Transgene.- II. Structure of the Human Immunoglobulin Loci.- 1. The Human ? Light Chain Locus.- 2. The Human ? Light Chain Locus.- 3. The Human Heavy Chain Locus.- D. Transgenic Technology.- I. Pronuclear Microinjection.- II. Embryonic Stem Cells.- III. Transgene Constructs.- 1. Bacteriophage Cloning Vectors.- 2. Plasmid Cloning Vectors.- 3. Yeast Artificial Chromosome Vectors.- E. Immunoglobulin Transgenics.- I. High Level and Cell Type Specific Expression.- 1. Cis-acting Regulatory Sequences.- 2. Transgene Expression.- 3. Human Transgene Constructs.- II. Rearrangement.- 1. Target Sequences.- 2. Immunoglobulin Gene Rearrangements in Transgenic Mice.- 3. Light Chain Junctions.- 4. Heavy Chain Junctions.- 5. Repercussions of Mouse B Cell Environment on Human VDJ Joints.- III. Allelic Exclusion.- 1. Background.- 2. Induction of Allelic Exclusion by Rearranged Transgenes.- 3. Response to Allelic Exclusion by Unrearranged Transgenes.- 4. Alternatives to Direct Feedback Allelic Exclusion.- IV. Primary Repertoire.- V. Intracellular Signaling.- 1. Background.- 2. B Cell Receptor Complex.- 1. Pre-B Cell Complex.- II. Class Switching.- 1. Background.- 2. Class Switching in Transgenic Mice.- 3. Importance of Class Switching for a Human Antibody Mouse.- III. Substrate for Somatic Mutation.- IV. Domination of the Immune Response.- 1. Antibody Depletion.- 2. Anti-sense Transgenes.- 3. Gene Targeting.- A. Perspective.- References.- Section II: Genetically Engineered Monoclonal Antibodies.- 4 Humanization of Monoclonal Antibodies.- A.

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