Strategies for Generating Diverse Antibody Repertoires Using Transgenic Animals Expressing Human Antibodies
| Autor: | Weihsu C. Chen, Christopher Murawsky |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
lcsh:Immunologic diseases. Allergy medicine.drug_class Transgene engineering Immunology Computational biology Biology Monoclonal antibody Antibodies diversity Animals Genetically Modified 03 medical and health sciences 0302 clinical medicine Immune system Antibody Repertoire antibody medicine Immunology and Allergy Animals Humans B cell transgenic B-Lymphocytes Drug discovery Repertoire repertoire therapeutic 030104 developmental biology medicine.anatomical_structure Antibody Formation Perspective biology.protein Antibody immune lcsh:RC581-607 030215 immunology |
| Zdroj: | Frontiers in Immunology Frontiers in Immunology, Vol 9 (2018) |
| ISSN: | 1664-3224 |
| Popis: | Therapeutic molecules derived from antibodies have become a dominant class of drugs used to treat human disease. Increasingly, therapeutic antibodies are discovered using transgenic animal systems that have been engineered to express human antibodies. While the engineering details differ, these platforms share the ability to raise an immune response that is comprised of antibodies with fully human idiotypes. Although the predominant transgenic host species has been mouse, the genomes of rats, rabbits, chickens, and cows have also been modified to express human antibodies. The creation of transgenic animal platforms expressing human antibody repertoires has revolutionized therapeutic antibody drug discovery. The observation that the immune systems of these animals are able to recognize and respond to a wide range of therapeutically relevant human targets has led to a surge in antibody-derived drugs in current development. While the clinical success of fully human monoclonal antibodies derived from transgenic animals is well established, recent trends have seen increasingly stringent functional design goals and a shift in difficulty as the industry attempts to tackle the next generation of disease-associated targets. These challenges have been met with a number of novel approaches focused on the generation of large, high-quality, and diverse antibody repertoires. In this perspective, we describe some of the strategies and considerations we use for manipulating the immune systems of transgenic animal platforms (such as XenoMouse®) with a focus on maximizing the diversity of the primary response and steering the ensuing antibody repertoire toward a desired outcome. |
| Databáze: | OpenAIRE |
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