Mesenchymal stem cells as a vehicle for targeted delivery of CRAds to lung metastases of breast carcinoma

Alternative and complementary therapeutic strategies need to be developed for metastatic breast cancer. Virotherapy is a novel therapeutic approach for the treatment of cancer in which the replicating virus itself is the anticancer agent. However, the success of virotherapy has been limited due to i...

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Bibliographic Details
Published in:	Breast cancer research and treatment Vol. 105; no. 2; pp. 157 - 167
Main Authors:	STOFF-KHALILI, Mariam A, RIVERA, Angel A, DOUGLAS, Joanne T, SIEGAL, Gene P, ZHU, Zeng B, BENDER, Hans Georg, DALL, Peter, STOW, Alexander, PEREBOEVA, Larissa, CURIEL, David T, MATHIS, J. Michael, SANJIB BANERJEE, N, MOON, Amanda S, HESS, A, ROCCONI, Rodney P, NUMNUM, T. Michael, EVERTS, M, CHOW, Louise T
Format:	Journal Article
Language:	English
Published:	Dordrecht Springer 01-10-2007 Springer Nature B.V
Subjects:	Adenoviridae - genetics Adenoviruses Animals Antineoplastic agents Biological and medical sciences Breast cancer Breast Neoplasms - genetics Breast Neoplasms - pathology Breast Neoplasms - therapy Cancer research Cancer therapies Female General aspects Genetic Therapy Genetic Vectors Gynecology. Andrology. Obstetrics Humans Lung Neoplasms - genetics Lung Neoplasms - secondary Lung Neoplasms - therapy Mammary gland diseases Medical sciences Mesenchymal Stromal Cells Mice Mice, SCID Pharmacology. Drug treatments Pneumology Promoter Regions, Genetic Receptors, CXCR4 - genetics Receptors, CXCR4 - metabolism Stem cells Survival Rate Therapy Transplantation, Heterologous Tumor Cells, Cultured Tumors Tumors of the respiratory system and mediastinum Lung disease Targeting Respiratory disease Stem cell Virotherapy Breast cancer Malignant tumor Metastasis Mesenchymal cell In vitro CRAds· Metastases Mammary gland diseases Breast carcinoma Cell vehicle Treatment Lung metastasis Stem cells Vector
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Summary:	Alternative and complementary therapeutic strategies need to be developed for metastatic breast cancer. Virotherapy is a novel therapeutic approach for the treatment of cancer in which the replicating virus itself is the anticancer agent. However, the success of virotherapy has been limited due to inefficient virus delivery to the tumor site. The present study addresses the utility of human mesenchymal stem cells (hMSCs) as intermediate carriers for conditionally replicating adenoviruses (CRAds) to target metastatic breast cancer in vivo. HMSC were transduced with CRAds. We used a SCID mouse xenograft model to examine the effects of systemically injected CRAd loaded hMSC or CRAd alone on the growth of MDA-MB-231 derived pulmonary metastases (experimental metastases model) in vivo and on overall survival. Intravenous injection of CRAd loaded hMSCs into mice with established MDA-MB-231 pulmonary metastatic disease homed to the tumor site and led to extended mouse survival compared to mice treated with CRAd alone. Injected hMSCs transduced with CRAds suppressed the growth of pulmonary metastases, presumably through viral amplification in the hMSCs. Thus, hMSCs may be an effective platform for the targeted delivery of CRAds to distant cancer sites such as metastatic breast cancer.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0167-6806 1573-7217
DOI:	10.1007/s10549-006-9449-8