NON-VIRAL DELIVERY OF INTERLEUKIN-2 AND SOLUBLE FLK-1 INHIBITS METASTATIC AND PRIMARY TUMOR GROWTH IN RENAL CELL CARCINOMA
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- Title
- NON-VIRAL DELIVERY OF INTERLEUKIN-2 AND SOLUBLE FLK-1 INHIBITS METASTATIC AND PRIMARY TUMOR GROWTH IN RENAL CELL CARCINOMA
- Authors
- Yockman, JW; Kim, WJ; Chang, CW; Kim, SW
- Date Issued
- 2007-10
- Publisher
- NATURE PUBLISHING GROUP
- Abstract
- Treatments for renal cell carcinoma, while promising, are still limited by toxicity and cost. In the hopes of finding a novel compound or combination, we developed a plasmid containing the genes for interleukin-2 (IL-2) and soluble vascular endothelial growth factor receptor 2 (msFlk1). The plasmid, p2CMVIL2/msFlk1, demonstrated similar in vitro transgene expression of IL-2 or msFlk1 compared to their single-agent counterparts. Subcutaneous tumor growth was significantly inhibited in the p2CMVIL2/msFlk1 group when delivered locally by the non-viral water soluble polymer, WSLP and exhibited a 50% increase in survival over glucose and single-agent controls. In vivo experimentation demonstrated that WSLP/msFlk1 decreased micro-vessel density in pCMVmsFlk1 and p2CMVIL2/msFlk1 treated groups. Furthermore, tumor-infiltrating lymphocytes expressing CD45RO and CD68 were increased within the tumor microenvironment upon p2CMVIL2/msFlk1 treatment. To determine the effects of p2CMVIL2/msFlk1 in an experimental RENCA lung metastases model, therapeutic DNA was delivered systemically following complexation with the angiogenic endothelial-targeting polymer PEI-g-PEG-RGD. The p2CMVIL2/msFlk1 treatment significantly reduced metastases by 56% over single-agent therapy and increased survival proportions by 50% over all groups. Our work clearly demonstrates that non-viral delivery of p2CMVIL2/msFlk1 can inhibit RENCA growth in a synergistic manner and may represent a new treatment for renal carcinoma.
- Keywords
- RECOMBINANT INTERLEUKIN-2; ANTITUMOR-ACTIVITY; GENE DELIVERY; T-CELLS; ENDOSTATIN; THERAPY; LYMPHOCYTES; COMBINATION; EXPRESSION; MURINE
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/28900
- DOI
- 10.1038/SJ.GT.330299
- ISSN
- 0969-7128
- Article Type
- Article
- Citation
- GENE THERAPY, vol. 14, no. 19, page. 1399 - 1405, 2007-10
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- There are no files associated with this item.
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