RT Journal Article
T1 In Vivo Tumor Targeting and Imaging with Engineered Trivalent Antibody Fragments Containing Collagen-Derived Sequences
A1 Cuesta Martínez, Ángel
A1 Sánchez-Martín, David
A1 Sanz, Laura
A1 Bonet, Jaume
A1 Compte, Marta
A1 Kremer, Leonor
A1 Blanco, Francisco J.
A1 Oliva, Baldomero
A1 Álvarez-Vallina, Luis
A2 Christophe Egles, 
AB There is an urgent need to develop new and effective agents for cancer targeting. In this work, a multivalent antibody is characterized in vivo in living animals. The antibody, termed “trimerbody”, comprises a single-chain antibody (scFv) fragment connected to the N-terminal trimerization subdomain of collagen XVIII NC1 by a flexible linker. As indicated by computer graphic modeling, the trimerbody has a tripod-shaped structure with three highly flexible scFv heads radially outward oriented. Trimerbodies are trimeric in solution and exhibited multivalent binding, which provides them with at least a 100-fold increase in functional affinity than the monovalent scFv. Our results also demonstrate the feasibility of producing functional bispecific trimerbodies, which concurrently bind two different ligands. A trimerbody specific for the carcinoembryonic antigen (CEA), a classic tumor-associated antigen, showed efficient tumor targeting after systemic administration in mice bearing CEA-positive tumors. Importantly, a trimerbody that recognizes an angiogenesis-associated laminin epitope, showed excellent tumor localization in several cancer types, including fibrosarcomas and carcinomas. These results illustrate the potential of this new antibody format for imaging and therapeutic applications, and suggest that some laminin epitopes might be universal targets for cancer targeting.
PB PLOS
YR 2009
FD 2009-04-29
LK https://hdl.handle.net/20.500.14352/93911
UL https://hdl.handle.net/20.500.14352/93911
LA eng
NO Cuesta AM, Sánchez-Martín D, Sanz L, et al. In vivo tumor targeting and imaging with engineered trivalent antibody fragments containing collagen-derived sequences. PLoS One. 2009;4(4):e5381. doi:10.1371/journal.pone.0005381
NO Ministerio de Ciencia e Innovación
NO Comunidad Autónoma de Madrid
NO Fundación Genoma España
NO Fondo de Investigación Sanitaria
DS Docta Complutense
RD 26 abr 2025