Cell carriers to deliver oncolytic viruses to sites of myeloma tumor growth

A. Munguia, T. Ota, T. Miest, Stephen J Russell

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Multiple myeloma (MM) is a disseminated malignancy of antibody secreting plasma cells that localize primarily to the bone marrow. Several studies have illustrated the potential of utilizing oncolytic viruses (measles, vaccinia, Vesicular Stomatitis Virus and coxsackievirus A21) for the treatment of MM, but there are significant barriers that prevent the viruses from reaching sites of myeloma tumor growth after intravenous delivery. The most important barriers are failure to extravasate from tumor blood vessels, mislocalization of the viruses in liver and spleen and neutralization by antiviral antibodies. In this review, we discuss the use of various cell types as carriers to overcome these barriers, emphasizing their relative susceptibilities to virus infection and their variable trafficking properties. Mesenchymal progenitor cells, monocytes and T cells have all shown promise as virus-delivery vehicles capable of accessing sites of myeloma growth. However, a previously unexplored alternative would be to use primary myeloma cells, or even myeloma cell lines, as delivery vehicles. Advantages of this approach are the natural ability of myeloma cells to home to sites of myeloma tumor growth and their compatibility with tumor-specific viruses that cannot propagate in other carrier cell lineages. A potential difficulty associated with the use of myeloma cells for virus delivery is that they must be exposed to supralethal doses of ionizing radiation before they can be safely administered to patients. Preliminary studies are presented in which we demonstrate the feasibility of using irradiated myeloma cells as carriers to deliver oncolytic viruses to sites of myeloma tumor growth in an orthotopic human myeloma model.

Original languageEnglish (US)
Pages (from-to)797-806
Number of pages10
JournalGene Therapy
Volume15
Issue number10
DOIs
StatePublished - May 2008

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Oncolytic Viruses
Viruses
Growth
Neoplasms
Multiple Myeloma
Vascular Tissue Neoplasms
Vaccinia
Antibody-Producing Cells
Oncogenic Viruses
Vesicular Stomatitis
Enterovirus
Measles
Cell Lineage
Virus Diseases
Ionizing Radiation
Plasma Cells
Mesenchymal Stromal Cells
Antiviral Agents
Monocytes
Spleen

ASJC Scopus subject areas

  • Genetics

Cite this

Cell carriers to deliver oncolytic viruses to sites of myeloma tumor growth. / Munguia, A.; Ota, T.; Miest, T.; Russell, Stephen J.

In: Gene Therapy, Vol. 15, No. 10, 05.2008, p. 797-806.

Research output: Contribution to journalArticle

Munguia, A. ; Ota, T. ; Miest, T. ; Russell, Stephen J. / Cell carriers to deliver oncolytic viruses to sites of myeloma tumor growth. In: Gene Therapy. 2008 ; Vol. 15, No. 10. pp. 797-806.
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