RT Journal Article
T1 Generation and characterization of monospecific and bispecific hexavalent trimerbodies
A1 Blanco Toribio, Ana
A1 Sainz Pastor, Noelia
A1 Álvarez Cienfuegos, Ana
A1 Merino, Nekane
A1 Sánchez Martín, David
A1 Bonet, Jaume
A1 Santos Valle, Patricia
A1 Sanz, Laura
A1 Oliva, Baldo
A1 Blanco, Francisco J.
A1 Álvarez Vallina, Luis
A1 Cuesta Martínez, Ángel
AB Here, we describe a new class of multivalent and multispecific antibody-based reagents for therapy. The molecules, termed “trimerbodies,” use a modified version of the N-terminal trimerization region of human collagen XVIII noncollagenous 1 domain flanked by two flexible linkers as trimerizing scaffold. By fusing single-chain variable fragments (scFv) with the same or different specificity to both N- and C-terminus of the trimerizing scaffold domain, we produced monospecific or bispecific hexavalent molecules that were efficiently secreted as soluble proteins by transfected mammalian cells. A bispecific anti-laminin x anti-CD3 N-/C-trimerbody was found to be trimeric in solution, very efficient at recognizing purified plastic-immobilized laminin and CD3 expressed at the surface of T cells, and remarkably stable in human serum. The bispecificity was further demonstrated in T cell activation studies. In the presence of laminin-rich substrate, the bispecific anti-laminin x anti-CD3 N-/C-trimerbody stimulated a high percentage of human T cells to express surface activation markers. These results suggest that the trimerbody platform offers promising opportunities for the development of the next-generation therapeutic antibodies, i.e., multivalent and bispecific molecules with a format optimized for the desired pharmacokinetics and adapted to the pathological context.
SN 1942-0862
YR 2013
FD 2013
LK https://hdl.handle.net/20.500.14352/93800
UL https://hdl.handle.net/20.500.14352/93800
LA eng
NO Blanco-Toribio A, Sainz-Pastor N, Álvarez-Cienfuegos A, et al. Generation and characterization of monospecific and bispecific hexavalent trimerbodies. MAbs. 2013;5(1):70-79. doi:10.4161/mabs.22698
NO Ministerio de Ciencia, Innovación e Universidades (España)
NO Ministerio de Economía y Competitividad (España)
NO Comunidad de Madrid
NO Instituto de Salud Carlos III
NO European Commission
NO Hospital Universitario Puerta de Hierro
DS Docta Complutense
RD 13 jul 2025