Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.jhep.2013.07.010
Title: Systemically delivered measles virus-infected mesenchymal stem cells can evade host immunity to inhibit liver cancer growth
Authors: Ong, H.-T.
Federspiel, M.J.
Guo, C.M.
Ooi, L.L.
Russell, S.J.
Peng, K.-W.
Hui, K.M. 
Keywords: Hepatocellular carcinoma
Human neutralizing antibody
Mesenchymal stem cells as cell delivery vehicles
Oncolytic measles virus
Orthotopically implanted HCC tumor model
Systemic virotherapy
Issue Date: Nov-2013
Citation: Ong, H.-T., Federspiel, M.J., Guo, C.M., Ooi, L.L., Russell, S.J., Peng, K.-W., Hui, K.M. (2013-11). Systemically delivered measles virus-infected mesenchymal stem cells can evade host immunity to inhibit liver cancer growth. Journal of Hepatology 59 (5) : 999-1006. ScholarBank@NUS Repository. https://doi.org/10.1016/j.jhep.2013.07.010
Abstract: Background & Aims Although attenuated measles virus (MV) has demonstrated potent oncolytic activities towards human cancers, it has not yet been widely adopted into clinical practice. One of the major hurdles is the presence of pre-existing anti-MV immunity in the recipients. In this study, we have evaluated the combination of the potent oncolytic activity of the attenuated MV with the unique immunoprivileged and tumor-tropic biological properties of human bone marrow-derived mesenchymal stem cells (BM-hMSCs) to combat human hepatocellular carcinoma (HCC), orthotopically implanted in SCID mice, passively immunized with human neutralizing antibodies against MV as a preclinical model. Methods SCID mice were orthotopically implanted with patient-derived HCC tissues and established HCC cell lines. SCID mice were passively immunized with human neutralizing anti-measles antibodies. Bioluminescence and fluorescence imaging were employed to monitor the ability of systemically delivered MV-infected BM-hMSCs to infiltrate the implanted tumors and their effects on tumor growth. Results Systemically delivered MV-infected BM-hMSCs homed to the HCC tumors implanted orthotopically in the liver and it was evidenced that BM-hMSCs could transfer MV infectivity to HCC via heterofusion. Furthermore, therapy with MV-infected BM-hMSCs resulted in significant inhibition of tumor growth in both measles antibody-naïve and passively-immunized SCID mice. By contrast, when cell-free MV viruses were delivered systemically, antitumor activity was evident only in measles antibody-naïve SCID mice. Conclusions MV-infected BM-hMSCs cell delivery system provides a feasible strategy to elude the presence of immunity against MV in most of the potential cancer patients to be treated with the oncolytic MV viruses.
Source Title: Journal of Hepatology
URI: http://scholarbank.nus.edu.sg/handle/10635/110294
ISSN: 01688278
DOI: 10.1016/j.jhep.2013.07.010
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