Systemic therapy of disseminated myeloma in passively immunized mice using measles virus-infected cell carriers

Research output: Contribution to journalArticle

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Abstract

Multiple myeloma (MM) is bone marrow plasma cell malignancy. A clinical trial utilizing intravenous administration of oncolytic measles virus (MV) encoding the human sodium-iodide symporter (MV-NIS) is ongoing in myeloma patients. However, intravenously administered MV-NIS is rapidly neutralized by antiviral antibodies. Because myeloma cell lines retain bone marrow tropism, they may be ideal as carriers for delivery of MV-NIS to myeloma deposits. A disseminated human myeloma (KAS 6/1) model was established. Biodistribution of MM1, a myeloma cell line, was determined after intravenous infusion. MM1 cells were found in the spine, femurs, and mandibles of tumor-bearing mice. Lethally irradiated MM1 cells remained susceptible to measles infection and transferred MV to KAS 6/1 cells in the presence of measles immune sera. Mice-bearing disseminated myeloma and passively immunized with measles immune serum were given MV-NIS or lethally irradiated MV-NIS-infected MM1 carriers. The antitumor activity of MV-NIS was evident only in measles naive mice and not in passively immunized mice. In contrast, survivals of both measles naive and immune mice were extended using MV-NIS-infected MM1 cell carriers. Hence, we demonstrate for the first time that systemically administered cells can serve as MV carriers and prolonged survival of mice with pre-existing antimeasles antibodies.

Original languageEnglish (US)
Pages (from-to)1155-1164
Number of pages10
JournalMolecular Therapy
Volume18
Issue number6
DOIs
StatePublished - Jun 2010

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Measles virus
Measles
Therapeutics
Immune Sera
Oncolytic Viruses
Cell Line
Tropism
Antibodies
Plasma Cells
Multiple Myeloma
Mandible
Intravenous Infusions
Bone Marrow Cells
Intravenous Administration
Femur
Antiviral Agents
Neoplasms
Spine
Bone Marrow
Clinical Trials

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Genetics
  • Drug Discovery
  • Pharmacology
  • Medicine(all)

Cite this

Systemic therapy of disseminated myeloma in passively immunized mice using measles virus-infected cell carriers. / Liu, Chunsheng; Russell, Stephen J; Peng, Kah-Whye.

In: Molecular Therapy, Vol. 18, No. 6, 06.2010, p. 1155-1164.

Research output: Contribution to journalArticle

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