Enhanced anti-tumor efficacy with multi-transgene armed mesenchymal stem cells for treating peritoneal carcinomatosis

Sep 22, 2026

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This study investigates whether intraperitoneally administered, non-virally engineered mesenchymal stem cells (MSCs) can co-deliver a CDUPRT/5-flucytosine prodrug system together with interferon-beta (IFNβ) to strengthen cGAS-STING signaling for peritoneal carcinomatosis. Engineered MSCs expressing CDUPRT or CDUPRT-IFNβ were validated by flow cytometry and ELISA, then assessed for anti-cancer effects in vitro and in vivo. Results show preserved MSC phenotypes and superior tumor growth inhibition with CDUPRT-IFNβ in both cell-line assays and an ES2 ovarian cancer xenograft model.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Background

Peritoneal carcinomatosis clinical context and treatment challenges

Methods

Intraperitoneal administration and engineered MSC design

Validation of transgene expression and experimental models

Results

MSC phenotype and migration after multi-transgene expression

In vitro and in vivo anti-tumor efficacy comparison

Conclusions

Potential foundation for clinical trial development

Ho etal. Journal of Translational Medicine (2024) 22:463 [https://doi.org/10.1186/s12967-024-05278-5](https://doi.org/10.1186/s12967-024-05278-5) Journal of Translational Medicine RESEARCH Open Access Enhanced anti-tumor efficacy with multi-transgene armed mesenchymal stem cells for treating peritoneal carcinomatosis Yoon Khei Ho 1,2,3,4* , Jun Yung Woo1,2, Kin Man Loke1,2, Lih‑Wen Deng 1,2 and Heng‑Phon Too1,2 Abstract Background Mesenchymal stem cells (MSCs) have garnered significant interest for their tumor‑tropic property, mak‑ ing them potential therapeutic delivery vehicles for cancer treatment. We have previously shown the significant anti‑ tumour activity in mice preclinical models and companion animals with naturally occurring cancers using non‑virally engineered MSCs with a therapeutic transgene encoding cytosine deaminase and uracil phosphoribosyl transferase (CDUPRT) and green fluorescent protein (GFP) . Clinical studies have shown improved response rate with combinato‑ rial treatment of 5‑fluorouracil and Interferon‑beta (IFNb) in peritoneal carcinomatosis (PC) . However, high systemic toxicities have limited the clinical use of such a regime. Methods In this study, we evaluated the feasibility of intraperitoneal administration of non‑virally engineered MSCsto co‑deliver CDUPRT/5‑Flucytosine prodrug system and IFNb to potentially enhance the cGAS‑STING signalling axis. Here, MSCs were engineered to express CDUPRT or CDUPRT‑IFNb. Expression of CDUPRT and IFNb was con‑ firmed by flow cytometry and ELISA, respectively. The anti‑cancer efficacy of the engineered MSCs was evaluated in both in vitro and in vivo model. ES2, HT‑29 and Colo‑205 were cocultured with engineered MSCs at various ratio. The cell viability with or without 5‑flucytosine was measured with MTS assay. To further compare the anti‑cancer efficacy of the engineered MSCs, peritoneal carcinomatosis mouse model was established by intraperitoneal injection of luciferase expressing ES2 stable cells. The tumour burden was measured through bioluminescence tracking. Results Firstly, there was no changes in phenotypes of MSCs despite high expression of the transgene encod‑ ing CDUPRT and IFNb (CDUPRT‑IFNb) . Transwell migration assays and in-vivo tracking suggested the co‑expression of multiple transgenes did not impact migratory capability ofthe MSCs. The superiority of CDUPRT‑IFNb over CDU‑ PRT expressing MSCs was demonstrated in ES2, HT‑29 and Colo‑205 in-vitro. Similar observations were observed in an intraperitoneal ES2 ovarian cancer xenograft model. The growth of tumor mass was inhibited by ~ 90% and 46% in the mice treated with MSCs expressing CDUPRT‑IFNb or CDUPRT, respectively. Conclusions Taken together, these results established the effectiveness of MSCs co‑expressing CDUPRT and IFNbin controlling and targeting PC growth. This study lay the foundation for the development of clinical trial using multigene‑armed MSCs for PC. Keywords Mesenchymal stem cells, Non‑viral gene modification, Peritoneal carcinomatosis *Correspondence: Yoon Khei Ho [bchhyk@nus.edu.sg](bchhyk@nus.edu.sg) Full list of author information is available at the end of the article © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

FAQs

What is the main therapeutic strategy tested in the study?

The study tests intraperitoneal administration of non-virally engineered MSCs that co-deliver a CDUPRT/5-flucytosine prodrug system and IFNβ to enhance cGAS-STING signaling against peritoneal carcinomatosis.

How were the engineered MSCs characterized to confirm expression?

CDUPRT expression and IFNβ production were confirmed using flow cytometry and ELISA, respectively.

What did the results show about the effectiveness of CDUPRT-IFNβ versus CDUPRT alone?

CDUPRT-IFNβ demonstrated superior anti-cancer efficacy in vitro across multiple cancer cell lines and similarly inhibited tumor growth in an intraperitoneal ES2 ovarian cancer xenograft model, compared with MSCs expressing CDUPRT only.

Sep 22, 2026

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