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

Mol Ther. 2010 Jun;18(6):1155-64. doi: 10.1038/mt.2010.43. Epub 2010 Mar 16.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • Chlorocebus aethiops
  • Humans
  • Immune Sera
  • Immunization, Passive*
  • Measles virus* / immunology
  • Mice
  • Mice, SCID
  • Multiple Myeloma / therapy*
  • Oncolytic Virotherapy*
  • Vero Cells

Substances

  • Antibodies, Neutralizing
  • Immune Sera