ORIGINAL RESEARCH article
Front. Bioeng. Biotechnol.
Sec. Cell and Gene Therapy
Volume 13 - 2025 | doi: 10.3389/fbioe.2025.1641137
This article is part of the Research TopicStem Cells and Kidney Regeneration: Transforming Renal MedicineView all 3 articles
A novel Frizzled 7 antibody that disrupts the Wnt pathway and inhibits Wilms tumor growth
Provisionally accepted
Einav Vax1,2Revital Caspi1,2,3
Rachel Shukrun1,2,3
Naomi Pode-Shakked1,2,3Oren Pleniceanu2,4,5Hana Golan1Michael Namestnikov2,4Michal Mark-Danieli1Ela Markovsky2Dekel D Bar-Lev4Iris Barshack4Ronit Satchi-Fainaro2Orit Harari- Steinberg4
Sanja Goldberg1,4*Benjamin Dekel1,2,4- 1Sheba Cancer Center, Sheba Medical Center, Tel Hashomer, Israel
- 2Tel Aviv University Faculty of Medical and Health Sciences, Tel Aviv-Yafo, Israel
- 3Dana-Dwek Children's Hospital Pediatrics Unit, Tel Aviv-Yafo, Israel
- 4Sheba Medical Center, Tel HaShomer, Israel
- 5Safra Children's Hospital, Sheba Medical Center, Israel, Ramat Gan, Israel
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The Frizzled 7 receptor, a Wnt receptor transducing Wnt/β-catenin signaling pathway, has long been implicated in a variety of adult and pediatric cancers, including Wilms tumor, the most common pediatric tumor of the kidney. We previously suggested that Frizzled 7 is a molecular marker of the cancer stem cell (CSC) population in Wilms tumor and may serve as a therapeutic target. In this work, using epitope mapping of the Frizzled 7 receptor, we created a cohort of specific monoclonal anti-Frizzled 7 antibodies. In this cohort, clone 288.1 induced significant cell death in primary Wilms tumor cells and inhibited cell proliferation and migration. This effect correlated with canonical Wnt signaling inhibition, a reduction in activated β-catenin and downregulation of Wnt/β-catenin target genes concomitant with diminished Wilms tumor CSC markers. Importantly, anti-FZD7-288.1 significantly inhibited growth of Wilms tumor xenografts tumor growth resulting in reduced tumor volume. Our results suggest that FZD7 is a valid therapeutic target in WT via an antibody mediated approach.
Keywords: Anti-Frizzled 7 antibody, Wilms Tumor, cancer stem cells, targeted therapy, Wnt/β-catenin signaling pathway
Received: 04 Jun 2025; Accepted: 28 Aug 2025.
Copyright: © 2025 Vax, Caspi, Shukrun, Pode-Shakked, Pleniceanu, Golan, Namestnikov, Mark-Danieli, Markovsky, Bar-Lev, Barshack, Satchi-Fainaro, Harari- Steinberg, Goldberg and Dekel. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Sanja Goldberg, Sheba Cancer Center, Sheba Medical Center, Tel Hashomer, Israel
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