期刊
JOURNAL OF HEPATOLOGY
卷 59, 期 5, 页码 999-1006出版社
ELSEVIER
DOI: 10.1016/j.jhep.2013.07.010
关键词
Systemic virotherapy; Oncolytic measles virus; Hepatocellular carcinoma; Orthotopically implanted HCC tumor model; Mesenchymal stem cells as cell delivery vehicles; Human neutralizing antibody
资金
- National Medical Research Council, Biomedical Research Council of Singapore
- Singapore Millennium Foundation
- SingHealth Foundation
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 hetero-fusion. Furthermore, therapy with MV-infected BM-hMSCs resulted in significant inhibition of tumor growth in both measles antibody-naive and passively-immunized SCID mice. By contrast, when cell-free MV viruses were delivered systemically, antitumor activity was evident only in measles antibody-naive 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. (C) 2013 European Association for the Study of the Liver. Published by Elsevier B. . All rights reserved.
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