Mesenchymal Stem Cells Expressing CES1 and Soluble TRAIL Activate CPT-11 and Induce Apoptosis in Lung Cancer Brain Metastatic Lesions
Kim DO., Jang EH., Kwon YD., Yoo JH., Ma X., Kim KH.
Prospective Study, published in Cancer Res Commun (2025) — summary generated from the PubMed abstract.
Early human evidence such as case series or small samples is exploring possible benefits.
- Level A · Stronger Clinical Evidence
- Level B · Emerging clinical evidence with positive signals
- Level C · Early human research exploring benefits
- Level D · Scientific groundwork from lab and animal studies
- Emerging · Emerging topic under active research
This page is generated from the PubMed record. The Thai description is an automated summary of bibliographic fields and the abstract, not a full translation, and is not medical advice.
- Study type
- Prospective Study
- Journal
- Cancer Res Commun (2025)
- Reported sample size
- —
- Source database
- Europe PMC
- PMID
- 40839370
- PMCID
- PMC12417980
- DOI
- 10.1158/2767-9764.crc-25-0209
Abstract (original English)
We aimed to develop a novel therapeutic strategy for lung cancer brain metastases by leveraging the tumor-tropic properties of genetically engineered Wharton's Jelly-derived mesenchymal stem cells (WJ-MSC) as vehicles for dual-agent gene therapy across the blood-brain barrier. WJ-MSCs were transiently engineered using lipid nanoparticle technology to coexpress soluble TRAIL (sTRAIL) and the prodrug-activating enzyme carboxylesterase 1 (CES1). In vitro analyses assessed transfection efficiency, therapeutic protein expression, apoptosis induction, and maintenance of stemness. Tumor-homing capacity was evaluated via EGFP labeling and intracerebral tracking. Therapeutic efficacy was tested in subcutaneous and intracerebral lung cancer xenograft models using bioluminescent imaging, histopathology, and IHC. In vivo treatment included intraperitoneal CPT-11 administration to assess synergy between CES1-mediated prodrug activation and sTRAIL-induced apoptosis. Modified WJ-MSCs exhibited preserved stem cell characteristics and strong tropism toward brain tumor sites. They secreted high levels of functional sTRAIL and CES1, enabling local activation of CPT-11 into SN-38 and inducing apoptosis through death receptor signaling (DR4/DR5). Combination therapy with WJ-MSCs-CES1.sTRAIL and CPT-11 significantly suppressed tumor growth in lung cancer brain metastasis models compared with control
What this study does not prove
- • This study does not prove SVF is an approved treatment or a replacement for standard care.
Evidence level
Early human evidence such as case series or small samples is exploring possible benefits.
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