Targeting the tumor vasculature with engineered cystine-knot miniproteins

Bonny Gaby Lui, Nadja Salomon, Joycelyn Wüstehube-Lausch, Matin Daneschdar, Hans-Ulrich Schmoldt, Özlem Türeci and Ugur Sahin ()
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Bonny Gaby Lui: BioNTech SE
Nadja Salomon: BioNTech SE
Joycelyn Wüstehube-Lausch: BioNTech SE
Matin Daneschdar: BioNTech SE
Hans-Ulrich Schmoldt: BioNTech SE
Özlem Türeci: BioNTech SE
Ugur Sahin: BioNTech SE

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: Abstract The extra domain B splice variant (EDB) of human fibronectin selectively expressed in the tumor vasculature is an attractive target for cancer imaging and therapy. Here, we describe the generation and characterization of EDB-specific optical imaging probes. By screening combinatorial cystine-knot miniprotein libraries with phage display technology we discover exquisitely EDB-specific ligands that share a distinctive motif. Probes with a binding constant in the picomolar range are generated by chemical oligomerization of selected ligands and fluorophore conjugation. We show by fluorescence imaging that the probes stain EDB in tissue sections derived from human U-87 MG glioblastoma xenografts in mice. Moreover, we demonstrate selective accumulation and retention of intravenously administered probes in the tumor tissue of mice with U-87 MG glioblastoma xenografts by in vivo and ex vivo fluorescence imaging. These data warrants further pursuit of the selected cystine-knot miniproteins for in vivo imaging applications.

Date: 2020
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DOI: 10.1038/s41467-019-13948-y

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