Measles vaccine strains for virotherapy of non-small-cell lung carcinoma

Manish R. Patel, Blake A. Jacobson, Holly Belgum, Ahmad Raza, Ahad Sadiq, Jeremy Drees, Hengbing Wang, Joseph Jay-Dixon, Ryan Etchison, Mark J. Federspiel, Stephen J. Russell, Robert A. Kratzke

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Introduction: Oncolytic virus therapy is a promising therapy for numerous tumor types. Edmonston-strain measles virus (MV) has been tested in clinical trials for ovarian cancer, glioma, and myeloma. Therefore, the antitumor activity of MV against non-small-cell lung cancer (NSCLC) was assessed. Methods: Human NSCLC cells and immortalized lung epithelial cell lines, Beas2B, were infected with either MV-producing green fluorescent protein or MV-producing carcinoembryonic antigen. Cells were assessed for viability, induction of apoptosis by caspase and poly-ADP ribose polymerase cleavage, and for viral transgene production. The dependency of MV entry on CD46 and nectin-4 were determined using blocking antibodies. The role of host translational activity on viral replication was assessed by overexpression of eIF4E and translation inhibition. Antitumor activity was assessed by measuring treated NSCLC xenografts from flanks of nude mice. Results: MV infection of NSCLC cells results in potent cell killing in most of the cell lines compared with immortalized Beas2B cells and induces apoptosis. MV infection was prevented by blocking of CD46, however independent of nectin-4 blockade. Tumor weights are diminished after intratumoral injections of MV-producing carcinoembryonic antigen in one of two cell lines and result in detectable viral transgene in serum of mice. Conclusions: These data indicate that MV is oncolytic for human NSCLC and this was independent of nectin-4 expression. Dysregulated protein translational machinery may play a role in determining tumor tropism in NSCLC. MV combined with gemcitabine could be explored further as chemovirotherapy for NSCLC.

Original languageEnglish (US)
Pages (from-to)1101-1110
Number of pages10
JournalJournal of Thoracic Oncology
Volume9
Issue number8
DOIs
StatePublished - Aug 2014

Keywords

  • Measles virus
  • Non-small-cell lung cancer
  • Translation

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

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    Patel, M. R., Jacobson, B. A., Belgum, H., Raza, A., Sadiq, A., Drees, J., Wang, H., Jay-Dixon, J., Etchison, R., Federspiel, M. J., Russell, S. J., & Kratzke, R. A. (2014). Measles vaccine strains for virotherapy of non-small-cell lung carcinoma. Journal of Thoracic Oncology, 9(8), 1101-1110. https://doi.org/10.1097/JTO.0000000000000214