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Blood, 1 October 2001, Vol. 98, No. 7, pp. 2002-2007
PLENARY PAPER
Systemic therapy of myeloma xenografts by an attenuated
measles virus
Kah-Whye Peng,
Gregory J. Ahmann,
Linh Pham,
Philip R. Greipp,
Roberto Cattaneo, and
Stephen J. Russell
From the Molecular Medicine Program and the Department
of Hematology, Mayo Foundation, Rochester, MN.
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-11and 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.
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