Identification of a novel CD40 ligand for targeted imaging of inflammatory plaques by phage display

Haixiang Yu, Filip Segers, Karen Sliedregt-Bol, Ilze Bot, Andrea M. Woltman, Peter Boross, Sjef Verbeek, Herman Overkleeft, Gijs A. van der Marel, Cees van Kooten, Theo J. C. van Berkel, Erik A. L. Biessen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

8 Citations (Web of Science)

Abstract

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.
Original languageEnglish
Pages (from-to)4136-4146
JournalFaseb Journal
Volume27
Issue number10
DOIs
Publication statusPublished - Oct 2013

Keywords

  • CD154
  • atherosclerosis
  • autoimmune diseases

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