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Systemic therapy of myeloma xenografts by an attenuated measles virus
1Molecular Medicine Program and the Department of Hematology, Mayo Foundation, Rochester, MN 55905, USA.
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.
Insights
The Edmonston-B strain of measles virus (MV-Edm) selectively replicates in multiple myeloma cells, demonstrating potent antitumor activity. This virus shows promise for treating multiple myeloma by causing tumor regression in preclinical models.
Area of Science:
- Oncolytic virotherapy
- Immunology
- Virology
Background:
- Conditionally replicating viruses offer a novel therapeutic strategy for malignancy.
- Measles virus (MV) strains are being investigated for their oncolytic potential.
Purpose of the Study:
- To evaluate the selective replication and antitumor efficacy of the live attenuated Edmonston-B strain of measles virus (MV-Edm) in human myeloma cells.
- To assess the in vitro and in vivo antineoplastic activity of MV-Edm against multiple myeloma.
Main Methods:
- In vitro studies involved infecting human myeloma cell lines and primary patient cells with MV-Edm, assessing replication and cytopathic effects.
- In vivo studies utilized immunocompromised mice with established human myeloma xenografts, evaluating antitumorigenic activity after direct injection or intravenous administration of MV-Edm.
Main Results:
- MV-Edm replicated efficiently in six human myeloma cell lines and primary myeloma cells, inducing significant cytopathic effects and syncytia formation.
- In contrast, MV-Edm replication was restricted in phytohemagglutinin-stimulated peripheral blood lymphocytes.
- In vivo, MV-Edm demonstrated potent antitumorigenic activity, leading to complete regression of established myeloma xenografts in mice, particularly the ARH-77 model.
Conclusions:
- MV-Edm exhibits selective replication in myeloma cells and potent in vivo antitumor activity.
- These findings support further development of MV-Edm as a potential therapeutic agent for multiple myeloma.