10.3389/fimmu.2018.03037.s002
Starlynn C. Clarke
Starlynn C.
Clarke
Biao Ma
Biao
Ma
Nathan D. Trinklein
Nathan
D. Trinklein
Ute Schellenberger
Ute
Schellenberger
Michael J. Osborn
Michael J.
Osborn
Laure-Hélène Ouisse
Laure-Hélène
Ouisse
Andrew Boudreau
Andrew
Boudreau
Laura M. Davison
Laura M.
Davison
Katherine E. Harris
Katherine E.
Harris
Harshad S. Ugamraj
Harshad S.
Ugamraj
Aarti Balasubramani
Aarti
Balasubramani
Kevin H. Dang
Kevin H.
Dang
Brett Jorgensen
Brett
Jorgensen
Heather Anne N. Ogana
Heather Anne N.
Ogana
Duy T. Pham
Duy T.
Pham
Payal P. Pratap
Payal P.
Pratap
Preethi Sankaran
Preethi
Sankaran
Ignacio Anegon
Ignacio
Anegon
Wim C. van Schooten
Wim C.
van Schooten
Marianne Brüggemann
Marianne
Brüggemann
Roland Buelow
Roland
Buelow
Shelley Force Aldred
Shelley
Force Aldred
Image_1_Multispecific Antibody Development Platform Based on Human Heavy Chain Antibodies.pdf
Frontiers
2019
heavy chain antibodies
VH domains
domain antibodies
antibody discovery platform
next-generation sequencing
repertoire sequencing
transgenic rats
B cell development
2019-01-07 04:15:01
Figure
https://frontiersin.figshare.com/articles/figure/Image_1_Multispecific_Antibody_Development_Platform_Based_on_Human_Heavy_Chain_Antibodies_pdf/7552370
<p>Heavy chain-only antibodies (HCAbs) do not associate with light chains and their V<sub>H</sub> regions are functional as single domains, forming the smallest active antibody fragment. These V<sub>H</sub> regions are ideal building blocks for a variety of antibody-based biologics because they tolerate fusion to other molecules and may also be attached in series to construct multispecific antibodies without the need for protein engineering to ensure proper heavy and light chain pairing. Production of human HCAbs has been impeded by the fact that natural human V<sub>H</sub> regions require light chain association and display poor biophysical characteristics when expressed in the absence of light chains. Here, we present an innovative platform for the rapid development of diverse sets of human HCAbs that have been selected in vivo. Our unique approach combines antibody repertoire analysis with immunization of transgenic rats, called UniRats, that produce chimeric HCAbs with fully human V<sub>H</sub> domains in response to an antigen challenge. UniRats express HCAbs from large transgenic loci representing the entire productive human heavy chain V(D)J repertoire, mount robust immune responses to a wide array of antigens, exhibit diverse V gene usage and generate large panels of stable, high affinity, antigen-specific molecules.</p>