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Targeting the tumor vasculature with engineered cystine-knot miniproteins

Author

Listed:
  • 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)

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.

Suggested Citation

  • Bonny Gaby Lui & Nadja Salomon & Joycelyn Wüstehube-Lausch & Matin Daneschdar & Hans-Ulrich Schmoldt & Özlem Türeci & Ugur Sahin, 2020. "Targeting the tumor vasculature with engineered cystine-knot miniproteins," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-13948-y
    DOI: 10.1038/s41467-019-13948-y
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    Cited by:

    1. Yan Zou & Yajing Sun & Yibin Wang & Dongya Zhang & Huiqing Yang & Xin Wang & Meng Zheng & Bingyang Shi, 2023. "Cancer cell-mitochondria hybrid membrane coated Gboxin loaded nanomedicines for glioblastoma treatment," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Zengping Duan & Chuilian Kong & Shihui Fan & Chuanliu Wu, 2024. "Triscysteine disulfide-directing motifs enabling design and discovery of multicyclic peptide binders," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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