Original Article
Cancer Gene Therapy (2007) 14, 819–827; doi:10.1038/sj.cgt.7701069; published online 13 July 2007
IL-12 gene-modified bone marrow cell therapy suppresses the development of experimental metastatic prostate cancer
H Wang1, G Yang1, T L Timme1, T Fujita1, K Naruishi1, A Frolov1, M K Brenner2, D Kadmon1 and T C Thompson1,3,4
- 1Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA
- 2Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA
- 3Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA
- 4Department of Radiology, Baylor College of Medicine, Houston, TX, USA
Correspondence: Dr TC Thompson, Scott Department of Urology, Baylor College of Medicine, 6560 Fannin, Suite 2100, Houston, TX 77030, USA. E-mail: timothyt@www.urol.bcm.tmc.edu
Received 29 November 2006; Revised 2 April 2007; Accepted 19 April 2007; Published online 13 July 2007.
Abstract
To investigate the immunomodulatory effects of interleukin-12 (IL-12) for treatment of metastatic prostate cancer, we administered adult bone marrow cells (BMC) that were genetically modified by retroviral vector-mediated IL-12 gene transduction in an experimental mouse model of prostate cancer metastasis. This therapy produced significant anti-metastatic effects in bone and lung and prolonged animal survival. Flow cytometric analysis indicated donor BMC could effectively home to bone and lung after treatment. Intensive infiltration of CD4 and CD8T cells in lung metastases and increased systemic natural killer and cytotoxic T lymphocyte activities indicated induction of a significant anti-metastatic immune response after treatment with IL-12 transduced BMC. Our results demonstrate the therapeutic potential of gene-modified BMC gene therapy.
Keywords:
IL-12, gene therapy, bone marrow cells, metastasis, cancer vaccination
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