6J7W

Crystal Structure of Human BCMA in complex with UniAb(TM) VH

Summary for 6J7W

• Entry DOI: 10.2210/pdb6j7w/pdb
• Descriptor: UniAb, Tumor necrosis factor receptor superfamily member 17 (3 entities in total)
• Functional Keywords: heavy chain antibodies, vh domains, domain antibodies, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 33889.46

Authors

Clarke, S.C.,Ma, B.,Trinklein, N.D.,Schellenberger, U.,Osborn, M.,Ouisse, L.,Boudreau, A.,Davison, L.,Harris, K.E.,Ugamraj, H.,Balasubramani, A.,Dang, K.,Jorgensen, B.,Ogana, H.,Pham, D.,Pratap, P.,Sankaran, P.,Anegon, I.,van Schooten, W.,Bruggemann, M.,Buelow, R.,Force Aldred, S. (deposition date: 2019-01-18, release date: 2019-02-06, Last modification date: 2023-11-22)

Primary citation

Clarke, S.C.,Ma, B.,Trinklein, N.D.,Schellenberger, U.,Osborn, M.J.,Ouisse, L.H.,Boudreau, A.,Davison, L.M.,Harris, K.E.,Ugamraj, H.S.,Balasubramani, A.,Dang, K.H.,Jorgensen, B.,Ogana, H.A.N.,Pham, D.T.,Pratap, P.P.,Sankaran, P.,Anegon, I.,van Schooten, W.C.,Bruggemann, M.,Buelow, R.,Force Aldred, S.
Multispecific Antibody Development Platform Based on Human Heavy Chain Antibodies
Front Immunol, 9:3037-3037, 2018

PubMed Abstract: Heavy chain-only antibodies (HCAbs) do not associate with light chains and their V regions are functional as single domains, forming the smallest active antibody fragment. These V 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 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 . Our unique approach combines antibody repertoire analysis with immunization of transgenic rats, called UniRats, that produce chimeric HCAbs with fully human V 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.

PubMed: 30666250
DOI: 10.3389/fimmu.2018.03037

Experimental method

X-RAY DIFFRACTION (2.6 Å)