Engineering oncolytic measles virus to circumvent the intracellular innate immune response

Iana Haralambieva, Ianko Iankov, Kosei Hasegawa, Mary Harvey, Stephen J Russell, Kah-Whye Peng

Research output: Contribution to journalArticle

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Abstract

The innate antiviral responses of tumor cells are often impaired but may still be sufficient to impede the intratumoral spread of an oncolytic virus. Here, we establish that the oncolytic measles virus (MV-eGFP) induces interferon (IFN) production in human myeloma and ovarian cancer cells. In addition, MV gene expression and virus progeny production were inhibited by IFN treatment of these tumor cells. The P gene of wild-type measles virus encodes P/V/C proteins known to antagonize IFN induction and/or response. We therefore engineered MV-eGFP for IFN evasion and more efficient intratumoral spread by arming it with the P gene from wild-type IC-B strain MV, thus generating MV-eGFP-Pwt. The chimeric virus exhibited reduced IFN sensitivity and diminished capacity to induce IFN in BJAB lymphoma, ARH-77 myeloma cells, and activated peripheral blood mononuclear cells. Interestingly, unlike the wild-type MV, MV-eGFP-Pwt was unable to shut down IFN induction completely. In immunocompromised mice bearing human myeloma xenografts, intravenously administered MV-eGFP-Pwt showed significantly enhanced oncolytic potency compared to MV-eGFP. These results indicate that oncolytic viruses are subject to control by the innate immune defenses of human tumor cells and may therefore be more effective if their natural ability to combat innate immunity is maintained.

Original languageEnglish (US)
Pages (from-to)588-597
Number of pages10
JournalMolecular Therapy
Volume15
Issue number3
DOIs
StatePublished - Mar 2007

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Oncolytic Viruses
Measles virus
Innate Immunity
Interferons
Viruses
Neoplasms
Protein C
Heterografts
Ovarian Neoplasms
Genes
Antiviral Agents
Lymphoma
Blood Cells
Gene Expression

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Engineering oncolytic measles virus to circumvent the intracellular innate immune response. / Haralambieva, Iana; Iankov, Ianko; Hasegawa, Kosei; Harvey, Mary; Russell, Stephen J; Peng, Kah-Whye.

In: Molecular Therapy, Vol. 15, No. 3, 03.2007, p. 588-597.

Research output: Contribution to journalArticle

Haralambieva, Iana ; Iankov, Ianko ; Hasegawa, Kosei ; Harvey, Mary ; Russell, Stephen J ; Peng, Kah-Whye. / Engineering oncolytic measles virus to circumvent the intracellular innate immune response. In: Molecular Therapy. 2007 ; Vol. 15, No. 3. pp. 588-597.
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