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8 - VelocImmune: Immunoglobulin Variable Region Humanized Mice

from PART III - TRANSGENIC HUMAN ANTIBODY REPERTOIRES

Published online by Cambridge University Press:  15 December 2009

By
Andrew Murphy
Edited by
Melvyn Little
Melvyn Little
Affiliation:
Affimed Therapeutics AG
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Summary

The study of immunology is inexorably linked to the practice of animal husbandry. For example, the word “vaccinate” is derived from the Latin vaccinus meaning “of or from cows.” The name stems from the practice of protecting people from the deadly smallpox virus by inoculating them with an extract derived from sores of cow udders infected with the innocuous cowpox virus. Later, the serum of animals that had been repeatedly exposed to sublethal doses of diptheria toxin was shown to protect humans against diphtheria, a discovery that eventually led to the discovery of antibodies. Eventually the study of antibody-producing cells in mice led to the invention of monoclonal antibody technology by Kohler and Milstein in 1975. Thus, it is no surprise that germline engineering of the mouse was put to immunological use soon after this powerful technology was developed. Here I describe the VelocImmune® mouse created several years ago by megabase-scale humanization of the variable portion of mouse immunoglobulin (Ig) loci, by far the largest such precision genome-engineering project to date, and compare it with other methods for the generation of humanized or fully human monoclonal antibody therapeutics.

ANTIBODY THERAPEUTICS

Monoclonal antibodies have numerous advantages as drugs. They possess the qualities of (1) high affinity and exquisite specificity leading to few off-target effects and generally superb safety profiles, (2) long half-life leading to infrequent dosing, and (3) reproducible physical characteristics leading to routine production and shortened development time lines.

Type
Chapter
Information
Recombinant Antibodies for Immunotherapy , pp. 100 - 108
Publisher: Cambridge University Press
Print publication year: 2009

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