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Enhanced anti-cancer activity of microglia by AAV2-mediated IL-12 in the therapy of glioblastoma multiforme

Tsung-Lang Chiu¹, Mei-Jen Wang² & Chin-Cheng Su³

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1. Division of Neuro-Oncology, Tzu-Chi Hospital
2. Department of Research, Tzu-Chi Hospital
3. Division of General Surgery, Tzu-Chi Hospital

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Document Type:

Manuscript

Date:

Received 20 April 2009 10:50 UTC; Posted 24 April 2009

Subjects:

Cancer

Tags:

• adeno-associated virus
• glioblastoma multiforme
• interleukin-12
• phagocytosis
• microglia
• TRAIL

Abstract:

Microglia has been found to diversify its function by cancerous cells or in a cancerous environment, thereby contributing to cancer growth and metastasis. Its immuno-activity, however, can be modulated by interleukin-12. So a strategy was designed using AAV2 carrying IL-12 to activate microglia then to eliminate cancerous cells. The transduction efficacy of AAV was evaluated with AAV2 encoding GFP and IL-12 on cancerous and CNS cells. The bioactivity of microglia modulated by IL-12 was examined and death receptors 4 and 5 were detected on cancerous cells. The effects of IL-12 and AAV2/IL-12 on microglial cytoxoxicity were evaluated too. The results demonstrated human cell line DBTRG, surgical specimen of GBM, and rat astrocyte expressed GFP quite well. Tremendous IL-12 secretion was detected in DBTRG, RG2, and astrocyte after transfection of AAV2/IL-12. TRAIL releasing and phagocytotic activity of microglia were significant, increasing (p<0.05) when the IL-12 protein or RG2-secreting IL-12 could have contact with microglial cells. Conclusively, AAV2 is an effective vector in transferring therapeutic genes such as IL-12 to induce or enhance microglial anti-cancer activity.

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1 comment

michal vure on 20 May 2009 09:58 UTC

I think it’s a very current subject.

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This document is licensed to the public under the Creative Commons Attribution 3.0 License

How to cite this document:

Chiu, Tsung-Lang, Wang, Mei-Jen, and Su, Chin-Cheng. Enhanced anti-cancer activity of microglia by AAV2-mediated IL-12 in the therapy of glioblastoma multiforme. Available from Nature Precedings <http://hdl.handle.net/10101/npre.2009.3101.1> (2009)

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