Strengthening of antitumor immune memory and prevention of thymic atrophy mediated by adenovirus expressing IL-12 and GM-CSF
- Title
- Strengthening of antitumor immune memory and prevention of thymic atrophy mediated by adenovirus expressing IL-12 and GM-CSF
- Author
- 윤채옥
- Keywords
- IL-12; GM-CSF; oncolytic adenovirus; RECURRENT PROSTATE-CANCER; ONCOLYTIC ADENOVIRUS; GENE-THERAPY; TUMOR-GROWTH; PHASE-I; THYMOCYTE PROLIFERATION; REPLICATION-COMPETENT; DENDRITIC CELLS; MURINE MAMMARY; BREAST-CANCER
- Issue Date
- 2012-10
- Publisher
- Nature Publishing Group
- Citation
- Gene Therapy, Jul 2012, 19(7), p711-723. 13p.
- Abstract
- Interleukin (IL)-12 and granulocyte-monocyte colony-stimulating factor (GM-CSF) have recently been used as immunotherapeutic agents in cancer gene therapy. IL-12 and GM-CSF have differential roles in the antitumor immune response, as IL-12 targets T, NK and natural killer T (NKT) cells and GM-CSF principally targets antigen-presenting cells (APCs). To strengthen the therapeutic efficacy of these two cytokines, we generated an oncolytic adenovirus (Ad), Ad-Delta B7/IL12/GMCSF, coexpressing IL-12 and GM-CSF. Using a murine B16-F10 syngeneic tumor model, we show that Ad-Delta B7/IL12/GMCSF promoted antitumor responses and increased survival compared with an oncolytic Ad expressing IL-12 or GM-CSF alone (Ad-Delta B7/IL12 or Ad-Delta B7/GMCSF, respectively). By measuring cytotoxic T lymphocyte activity and interferon-gamma production, we show that the enhanced therapeutic effect was mediated by the induction of immune cell cytotoxicity. In situ delivery of Ad-Delta B7/IL12/GMCSF resulted in massive infiltration of CD4(+) T cells, CD8(+) T cells, NK cells and CD86(+) APCs into the tissue surrounding the necrotic area of the tumor. Moreover, GM-CSF effectively promoted antitumor immune memory, which was significantly augmented by IL-12. Lastly, IL12-expressing oncolytic Ads prevented tumor-induced thymic atrophy and was associated with reduced apoptosis and increased proliferation in the thymus. Taken together, these data demonstrate that an oncolytic Ad coexpressing IL-12 and GM-CSF is a potential therapeutic tool for the treatment of cancer. Gene Therapy (2012) 19, 711-723; doi:10.1038/gt.2011.125; published online 13 October 2011
- URI
- https://www.nature.com/articles/gt2011125http://hdl.handle.net/20.500.11754/67610
- ISSN
- 0969-7128
- DOI
- 10.1038/gt.2011.125
- Appears in Collections:
- COLLEGE OF ENGINEERING[S](공과대학) > BIOENGINEERING(생명공학과) > Articles
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