Anti-tumor effects of canine adipose tissue-derived mesenchymal stromal cell-based interferon-β gene therapy and cisplatin in a mouse melanoma model.

Abstract

BACKGROUND AIMS:

Adipose tissue (AT)-derived mesenchymal stromal cells (MSC) (AT-MSC) represent a novel tool for delivering therapeutic genes to tumor cells. Interferon (IFN)-β is a cytokine with pleiotropic cellular functions, including anti-proliferative, immunomodulatory and anti-angiogenic activities. The purpose of this study was to engineer canine AT-MSC (cAT-MSC) producing IFN-β and to evaluate the anti-tumor effect of cAT-MSC-IFN-β combined with cisplatin in mouse melanoma model.

METHODS:

cAT-MSC engineered to express mouse IFN-β were generated using a lentiviral vector (cAT-MSC-IFN-β) and the secreted IFN-β-induced inhibition of tumor cell growth and apoptosis on B16F10 cells was investigated in vitro prior to in vivo studies. Melanoma-bearing mouse was developed by injecting B16F10 cells subcutaneously into 6-week-old C57BL/6 mice. After 14 days, cisplatin (10 mg/kg) was injected intratumorally, and 3 days later the engineered cAT-MSC were injected subcutaneously every 3 days to death. Tumor volume and survival times were measured.

RESULTS:

The combination treatment of cAT-MSC-IFN-β with cisplatin was more effective in inhibiting the growth of melanoma and resulted in significantly extended survival time than both an unengineered cAT-MSC-cisplatin combination group and a cisplatin-alone group. Interestingly, subcutaneously injected cAT-MSC-IFN-β were migrated to tumor sites.

CONCLUSIONS:

Our data suggest that canine AT-MSC could serve as a powerful cell-based delivery vehicle for releasing therapeutic proteins to tumor lesions. Maximal anti-tumor effects were seen when this therapy was combined with a DNA-damaging chemotherapeutic agent. This study demonstrates the possible applicability of AT-MSC-mediated IFN-β in treating canine and human cancer patients.

• Authors: Kyoung-Won Seo, Hee-Woo Lee, Ye-In Oh, Jin-Ok Ahn, Ye-Rin Koh, Seung-Hyun Oh, Sung-Keun Kang, Hwa-Young Youn
• Journal: Cytotherapy (Cytotherapy) Vol. 13 Issue 8 Pg. 944-55 (Sep 2011) ISSN: 1477-2566 [Electronic] England
• PMID: 21846298 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interferon-beta
• Cisplatin

Topics

• Adipose Tissue (cytology)
• Animals
• Cell Growth Processes (drug effects)
• Cell Movement
• Cisplatin (administration & dosage)
• Disease Models, Animal
• Dogs
• Drug Delivery Systems
• Genetic Engineering
• Genetic Therapy
• Humans
• Interferon-beta (genetics, immunology, metabolism)
• Melanoma, Experimental (genetics, pathology, therapy)
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells (cytology, metabolism)
• Mice
• Mice, Inbred C57BL
• Stem Cell Transplantation
• Tumor Burden