Multispecific Antibody Development Platform Based on Human Heavy Chain Antibodies.

Autor:	Clarke SC; Teneobio, Inc., Menlo Park, CA, United States., Ma B; Teneobio, Inc., Menlo Park, CA, United States., Trinklein ND; Teneobio, Inc., Menlo Park, CA, United States., Schellenberger U; Teneobio, Inc., Menlo Park, CA, United States., Osborn MJ; Teneobio, Inc., Menlo Park, CA, United States., Ouisse LH; Centre de Recherche en Transplantation et Immunologie, Inserm UMR 1064, Université de Nantes, Nantes, France., Boudreau A; Teneobio, Inc., Menlo Park, CA, United States., Davison LM; Teneobio, Inc., Menlo Park, CA, United States., Harris KE; Teneobio, Inc., Menlo Park, CA, United States., Ugamraj HS; Teneobio, Inc., Menlo Park, CA, United States., Balasubramani A; Teneobio, Inc., Menlo Park, CA, United States., Dang KH; Teneobio, Inc., Menlo Park, CA, United States., Jorgensen B; Teneobio, Inc., Menlo Park, CA, United States., Ogana HAN; Teneobio, Inc., Menlo Park, CA, United States., Pham DT; Teneobio, Inc., Menlo Park, CA, United States., Pratap PP; Teneobio, Inc., Menlo Park, CA, United States., Sankaran P; Teneobio, Inc., Menlo Park, CA, United States., Anegon I; Centre de Recherche en Transplantation et Immunologie, Inserm UMR 1064, Université de Nantes, Nantes, France., van Schooten WC; Teneobio, Inc., Menlo Park, CA, United States., Brüggemann M; Teneobio, Inc., Menlo Park, CA, United States., Buelow R; Teneobio, Inc., Menlo Park, CA, United States., Force Aldred S; Teneobio, Inc., Menlo Park, CA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2019 Jan 07; Vol. 9, pp. 3037. Date of Electronic Publication: 2019 Jan 07 (Print Publication: 2018).
DOI:	10.3389/fimmu.2018.03037
Abstrakt:	Heavy chain-only antibodies (HCAbs) do not associate with light chains and their V H regions are functional as single domains, forming the smallest active antibody fragment. These V H 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 H 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 H 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.
Databáze:	MEDLINE
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