Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Aug 13:e15356.
doi: 10.1002/advs.202415356. Online ahead of print.

Systematic Targeting of GD2-Positive Neuroblastoma Tumors With a Photooncolytic Phage Nanovector Platform

Suleman Khan Zadran  1   2   3 , Nicola Facchinello  1   4 , Piergiuseppe De Rosa  1 , Roberto Saporetti  5 , Paolo Emidio Costantini  1   2 , Luca Ulfo  1 , Michela Nigro  1   2 , Annapaola Petrosino  1 , Lucia Pappagallo  1 , Sara Aloisi  1 , Giorgio Milazzo  1 , Zainul Abe Din  1 , Alberto Rigamonti  1 , Leonardo Flora  1 , Martina Santulli  1 , Leonardo Cimadom  1 , Giampaolo Zuccheri  1 , Mattia Zangoli  6 , Manuele Di Sante  5 , Matteo Di Giosia  5   2 , Francesca Di Maria  6 , Roberto Bernardoni  1 , Eveline Barbieri  3 , Matteo Calvaresi  5   2 , Alberto Danielli  1   2 , Giovanni Perini  1   2
Affiliations

Systematic Targeting of GD2-Positive Neuroblastoma Tumors With a Photooncolytic Phage Nanovector Platform

Suleman Khan Zadran et al. Adv Sci (Weinh). .

Abstract

Disialoganglioside-GD2 is a key molecular target for Neuroblastoma (NB) immunotherapy based on the employment of GD2-targeting antibodies. However, about 50% of treated patients can experience tumor relapse due to limited immune-mediated cytotoxicity and poor antibody penetration into tumors. To address this problem, a tumor-penetrating photo-oncolytic phage nanovector platform is genetically and chemically developed that selectively targets GD2-expressing NB cells. The phage bioconjugates, functionalized with different photosensitizers, result in specific and selective oncolysis of GD2-positive NB cells upon light irradiation, without affecting GD2-negative ones. The photo-oncolytic phage vectors are shown to deeply penetrate into GD2-positive tumor spheroids in vitro, and to cross biological barriers in a zebrafish xenograft model, maintaining their ablation specificity upon irradiation. Finally, to overcome resistance from GD2 loss, often linked to poor prognosis, a CRISPRa strategy is introduced to reactivate GD2 expression in GD2-negative cells. The approach offers a minimally invasive and highly effective strategy, addressing unmet needs in NB therapy.

Keywords: CRISPRa; M13 bacteriophage biotherapeutics; neuroblastoma GD2; photodynamic therapy; zebrafish xenograft.

PubMed Disclaimer

References

    1. a) K. K. Matthay, J. M. Maris, G. Schleiermacher, A. Nakagawara, C. L. Mackall, L. Diller, W. A. Weiss, Nat. Rev.: Dis. Prim. 2016, 2.
    1. b) E. Steliarova‐Foucher, M. Colombet, L. A. Ries, F. Moreno, A. Dolya, F. Bray, P. Hesseling, H. Y. Shin, C. A. Stiller, Lancet Oncol. 2017, 18, 719.
    1. a) N. A. Shendy, M. W. Zimmerman, B. J. Abraham, A. D. Durbin, Cell Rep. Med. 2022, 3, 100632;
    1. b) E. Rodriguez‐Fos, M. Planas‐Fèlix, M. Burkert, M. Puiggròs, J. Toedling, N. Thiessen, E. Blanc, A. Szymansky, F. Hertwig, N. Ishaque, D. Beule, D. Torrents, A. Eggert, R. P. Koche, R. F. Schwarz, K. Haase, J. H. Schulte, A. G. Henssen, Cell Genom. 2023, 3, 100402.
    1. L. Amoroso, R. Haupt, A. Garaventa, M. Ponzoni, Expert Opin. Invest. Drugs 2017, 26, 1281.