Systemic therapy of myeloma xenografts by an attenuated measles virus

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Abstract
Conditionally replicating viruses are promising agents for the treatment of malignancy. Here it is shown that the live attenuated Edmonston-B vaccine strain of measles virus (MV-Edm) replicates selectively in human myeloma cells and has potent antitumor activity. In vitro, replication of MV-Edm was restricted in phytohemagglutinin (PHA)-stimulated peripheral blood lymphocytes (PBLs) but proceeded efficiently in a panel of 6 myeloma cell lines—ARH-77, RPMI 8226, JJN-3, MM1, KAS-6/1, and KMS-11—and in primary myeloma cells isolated by CD138 sorting from the bone marrow aspirates of 6 patients. MV-Edm infection induced potent cytopathic effects in these myeloma cells, resulting in the formation of multinucleated syncytia that eventually became nonviable. In contrast, syncytial formation in PHA-stimulated PBLs was minimal after MV-Edm infection. In vivo, MV-Edm was antitumorigenic and inhibited the establishment of myeloma cells as xenografts in immunocompromised mice. When injected directly into ARH-77 myeloma xenografts in the mice, MV-Edm caused complete regression of these xenografts. MV-Edm administered intravenously into the tail veins of mice also showed significant antineoplastic activity against established RPMI 8226 and ARH-77 xenografts. In particular, the ARH-77 myeloma xenografts were exquisitely sensitive to MV-Edm therapy, and tumors in all mice regressed completely. In light of its selectivity for myeloma cells and its potent antineoplastic activity against myeloma xenografts in vivo, MV-Edm merits further development for the treatment of multiple myeloma.