Book contents
- Frontmatter
- Contents
- Contributors
- Foreword by Sir Gregory Winter
- Preface
- RECOMBINANT ANTIBODIES FOR IMMUNOTHERAPY
- PART I HUMANIZED ANTIBODIES
- PART II GENERATION AND SCREENING OF ANTIBODY LIBRARIES
- PART III TRANSGENIC HUMAN ANTIBODY REPERTOIRES
- PART IV ANTIBODY EFFECTOR FUNCTION
- PART V ARMING ANTIBODIES
- PART VI NOVEL ANTIBODY FORMATS
- PART VII ANTIGEN-BINDING REPERTOIRES OF NON-IMMUNOGLOBULIN PROTEINS
- 18 Alternative Scaffolds: Expanding the Options of Antibodies
- PART VIII PROLONGATION OF SERUM HALF-LIFE
- PART IX INNOVATIVE IMMUNOTHERAPEUTIC APPROACHES
- PART X MARKET OVERVIEW AND OUTLOOK
- Index
- Plate section
- References
18 - Alternative Scaffolds: Expanding the Options of Antibodies
from PART VII - ANTIGEN-BINDING REPERTOIRES OF NON-IMMUNOGLOBULIN PROTEINS
Published online by Cambridge University Press: 15 December 2009
- Frontmatter
- Contents
- Contributors
- Foreword by Sir Gregory Winter
- Preface
- RECOMBINANT ANTIBODIES FOR IMMUNOTHERAPY
- PART I HUMANIZED ANTIBODIES
- PART II GENERATION AND SCREENING OF ANTIBODY LIBRARIES
- PART III TRANSGENIC HUMAN ANTIBODY REPERTOIRES
- PART IV ANTIBODY EFFECTOR FUNCTION
- PART V ARMING ANTIBODIES
- PART VI NOVEL ANTIBODY FORMATS
- PART VII ANTIGEN-BINDING REPERTOIRES OF NON-IMMUNOGLOBULIN PROTEINS
- 18 Alternative Scaffolds: Expanding the Options of Antibodies
- PART VIII PROLONGATION OF SERUM HALF-LIFE
- PART IX INNOVATIVE IMMUNOTHERAPEUTIC APPROACHES
- PART X MARKET OVERVIEW AND OUTLOOK
- Index
- Plate section
- References
Summary
In the language of modern biotechnology, monoclonal antibodies (Köhler & Milstein,1975) were the first “library” of proteins that was available, and the immune system was the first “selection” technology by which a specific binder could be obtained. However, only the subsequent introduction of molecular biology into this field allowed a true control over the molecules (reviewed, e.g., in Plückthun & Moroney, 2005; Weiner & Carter, 2003). This development of technologies was largely driven by the desire to use antibodies therapeutically, since the extraordinarily strong immune response to a nonhuman antibody in humans had put an end to essentially all of these endeavors. As will be illustrated in the following paragraphs, technological developments intended to solve this problem made not only the use of an animal immune system, but, ironically, also the antibody molecule itself dispensable.
Three fundamental approaches have been developed to arrive at antibody molecules that are able to evade the human immune surveillance and which, at least from this perspective, may become potential therapeutics. The first approach, termed “humanization” (Jones et al., 1986), converts an existing murine antibody obtained by immunization into an analogous one with as much human sequence as possible. Another approach, a technical tour de force, was to introduce human antibody genes into a mouse and inactivate or delete the murine loci, such that an immunized mouse would then produce antibodies after immunization that essentially consisted of human sequences (Fishwild et al., 1996; Mendez et al., 1997).
- Type
- Chapter
- Information
- Recombinant Antibodies for Immunotherapy , pp. 243 - 272Publisher: Cambridge University PressPrint publication year: 2009
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