Novel therapies show promise against myeloi...( (IFN) the IFN-MSC directly inhibited ...)

(IFN), the IFN-MSC directly inhibited the growth of both melanoma and breast carcinoma cells in experiments in vitro (in tissue cultures). When researchers intravenously (IV) injected IFN-MSC (four doses of 106 MSC/week) into mice with metastatic lung cancers, tumor growth was inhibited and survival of the animals doubled. A key finding was that IV-injected MSC hone and proliferate selectively in the stroma and metastases of tumors, and have the potential to produce therapeutic agents locally. MSC were also found to be capable of delivering replication-competent oncolytic adenovirus (delta24, a virus capable of destructing tumor cells) into tumors. Thus, MSC act as "Trojan horses" that carry therapeutic genes into the tumors. In contrast, when IFN was injected subcutaneously, no tumor inhibition was observed.

Similar results were seen after intraperitoneal injections (into the lining of the abdominal cavity) of IFN-MSC into mice with ovarian cancer, doubling survival in SKOV-3 and curing 70 percent of mice with OVAR-3 cancers. Interestingly, MSC injected into the carotid artery of mice with malignant gliomas (incurable brain tumors) reproduced selectively in the tumors, and not in normal brain tissues. Tumor growth was inhibited by co-cultures of IFN-MSC and glioma cells in vitro, and injection of IFN-MSC directly into the tumor in vivo. In a model of very aggressive chronic myeloid leukemia in blast crisis, MSC-produced interferon alpha (IFNaMSC) inhibited tumor growth in vivo and doubled the survival rates of CML bearing mice.

"These findings indicate that mesenchymal stem cells can deliver interferons, oncolytic adenovirus, and perhaps other therapeutic agents directly into tumor and leukemia sites," said Michael Andreeff, M.D., Ph.D., of the M.D. Anderson Cancer Center, lead author of the study. "MSC appear to selectively grow and deliver payload at tumor sites, suggesting strong potential of gene-
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Contact: Aimee Frank
amf@spectrumscience.com
202-955-6222
American Society of Hematology
6-Dec-2003

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