TY - JOUR
T1 - Identification of a novel CD40 ligand for targeted imaging of inflammatory plaques by phage display
AU - Yu, Haixiang
AU - Segers, Filip
AU - Sliedregt-Bol, Karen
AU - Bot, Ilze
AU - Woltman, Andrea M.
AU - Boross, Peter
AU - Verbeek, Sjef
AU - Overkleeft, Herman
AU - van der Marel, Gijs A.
AU - van Kooten, Cees
AU - van Berkel, Theo J. C.
AU - Biessen, Erik A. L.
PY - 2013/10
Y1 - 2013/10
N2 - The CD40/CD40L dyad is deemed to play a central role in several inflammatory processes, including atherosclerosis. As CD40 is overexpressed in atherosclerotic lesions, it constitutes a promising candidate for targeted imaging approaches. Here we describe the design of a novel, selective peptide ligand for CD40 by phage display. A synthetic peptide corresponding with the phage insert NP31 displayed nanomolar affinity for CD40. Affinity was further enhanced by mutimeric presentation of NP31. An essential 11-mer peptide motif was identified by truncation and alanine scan studies. Enriched phage selectively bound human CD40 and homed to inflammatory joints in a murine model of rheumatoid arthritis. NP31 ablated VEGF and IL-6 transcriptional activation and partially inhibited IL-6 production by CD40L-activated endothelial cells. Notably, NP31 did not only alter the biodistribution profile of a streptavidin scaffold but also markedly increased accumulation of the carrier in atherosclerotic aortic lesions of aged ApoE(-/-) mice in a CD40-dependent manner. This potent and selective peptide ligand has potential for targeted imaging and drug delivery approaches in CD40-dependent inflammatory disorders such as atherosclerosis.Yu, H., Segers, F., Sliedregt-Bol, K., Bot, I., Woltman, A. M.(,) Boross, P., Verbeek, S., Overkleeft, H., van der Marel, G. A., van Kooten, C., van Berkel, T. J. C., Biessen, E. A. L. Identification of a novel CD40 ligand for targeted imaging of inflammatory plaques by phage display.
AB - The CD40/CD40L dyad is deemed to play a central role in several inflammatory processes, including atherosclerosis. As CD40 is overexpressed in atherosclerotic lesions, it constitutes a promising candidate for targeted imaging approaches. Here we describe the design of a novel, selective peptide ligand for CD40 by phage display. A synthetic peptide corresponding with the phage insert NP31 displayed nanomolar affinity for CD40. Affinity was further enhanced by mutimeric presentation of NP31. An essential 11-mer peptide motif was identified by truncation and alanine scan studies. Enriched phage selectively bound human CD40 and homed to inflammatory joints in a murine model of rheumatoid arthritis. NP31 ablated VEGF and IL-6 transcriptional activation and partially inhibited IL-6 production by CD40L-activated endothelial cells. Notably, NP31 did not only alter the biodistribution profile of a streptavidin scaffold but also markedly increased accumulation of the carrier in atherosclerotic aortic lesions of aged ApoE(-/-) mice in a CD40-dependent manner. This potent and selective peptide ligand has potential for targeted imaging and drug delivery approaches in CD40-dependent inflammatory disorders such as atherosclerosis.Yu, H., Segers, F., Sliedregt-Bol, K., Bot, I., Woltman, A. M.(,) Boross, P., Verbeek, S., Overkleeft, H., van der Marel, G. A., van Kooten, C., van Berkel, T. J. C., Biessen, E. A. L. Identification of a novel CD40 ligand for targeted imaging of inflammatory plaques by phage display.
KW - CD154
KW - atherosclerosis
KW - autoimmune diseases
U2 - 10.1096/fj.12-224667
DO - 10.1096/fj.12-224667
M3 - Article
C2 - 23896727
SN - 0892-6638
VL - 27
SP - 4136
EP - 4146
JO - Faseb Journal
JF - Faseb Journal
IS - 10
ER -