Enhanced antitumor effects of an engineered measles virus edmonston strain expressing the wild-type N, P, L genes on human renal cell carcinoma

Xin Meng, Takafumi Nakamura, Toshihiko Okazaki, Hiroyuki Inoue, Atsushi Takahashi, Shohei Miyamoto, Gaku Sakaguchi, Masatoshi Eto, Seiji Naito, Makoto Takeda, Yusuke Yanagi, Kenzaburo Tani

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27 Citations (Scopus)

Abstract

Measles virus Edmonston strain (MV-Edm) is thought to have remarkable oncolytic activity that selectively destroys human tumor cells. The P/V/C protein of wild-type MV was shown to resist the antiviral effects of interferon (IFN)-α. Here, we engineered new MVs by arming MV-Edm tag strain (a V-defective vaccine-lineage strain, MV-Etag) with the P or N, P, and L genes of wild-type MV (MV-P and MV-NPL, respectively). The oncolytic activities of the MVs were determined in human renal cell carcinoma (RCC) cell lines and primary human RCC cells by the MTT assay. The antitumor efficacy of the MVs was evaluated in A-498 xenografts in nude mice. IFN-α effectively inhibited the replication of MV-Etag and MV-P, but not MV-NPL. MV-NPL more efficiently induced cytopathic effects (CPEs) in OS-RC-2 cells, even in the presence of human IFN-α. MV-NPL replicated more rapidly than MV-P and MV-Etag in A-498 cells. Apoptosis was induced earlier in A-498 cells by MV-NPL than MV-Etag and MV-P. MV-NPL showed more significant antitumoral effects and had prolonged replication compared to MV-Etag and MV-P. In this study, we demonstrated that the newly engineered MV-NPL has more effective oncolytic activity and may help establish an innovative cancer therapy.

Original languageEnglish
Pages (from-to)544-551
Number of pages8
JournalMolecular Therapy
Volume18
Issue number3
DOIs
Publication statusPublished - Mar 2010

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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    Meng, X., Nakamura, T., Okazaki, T., Inoue, H., Takahashi, A., Miyamoto, S., Sakaguchi, G., Eto, M., Naito, S., Takeda, M., Yanagi, Y., & Tani, K. (2010). Enhanced antitumor effects of an engineered measles virus edmonston strain expressing the wild-type N, P, L genes on human renal cell carcinoma. Molecular Therapy, 18(3), 544-551. https://doi.org/10.1038/mt.2009.296