Language
English
Publication Date
10-1-2025
Journal
Advanced Science
DOI
10.1002/advs.202415356
PMID
40799139
PMCID
PMC12520574
PubMedCentral® Posted Date
8-13-2025
PubMedCentral® Full Text Version
Post-print
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
Neuroblastoma, Humans, Animals, Zebrafish, Gangliosides, Cell Line, Tumor, Bacteriophages, Oncolytic Virotherapy, Photochemotherapy, Photosensitizing Agents, CRISPRa, M13 bacteriophage biotherapeutics, neuroblastoma GD2, photodynamic therapy, zebrafish xenograft
Published Open-Access
yes
Recommended Citation
Zadran, Suleman Khan; Facchinello, Nicola; De Rosa, Piergiuseppe; et al., "Systematic Targeting of GD2-Positive Neuroblastoma Tumors With a Photooncolytic Phage Nanovector Platform" (2025). Faculty, Staff and Students Publications. 6301.
https://digitalcommons.library.tmc.edu/baylor_docs/6301