Systemic therapy of disseminated myeloma in passively immunized mice using measles virus-infected cell carriers.
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.
Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
Chunsheng
C
Liu
Stephen J
SJ
Russell
Kah-Whye
KW
Peng
D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D002522:Chlorocebus aethiops; D006801:Humans; D007106:Immune Sera; D007116:Immunization, Passive; D008459:Measles virus / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D009101:Multiple Myeloma / Q000628:therapy*; D050130:Oncolytic Virotherapy; D014709:Vero Cells
D057134:Antibodies, Neutralizing; D007106:Immune Sera