RGD Reference Report - Non-viral delivery of interleukin-2 and soluble Flk-1 inhibits metastatic and primary tumor growth in renal cell carcinoma. - Rat Genome Database

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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 
Citation: Yockman JW, etal., Gene Ther. 2007 Oct;14(19):1399-405. Epub 2007 Jul 26.
RGD ID: 2301756
Pubmed: PMID:17653245   (View Abstract at PubMed)
DOI: DOI:10.1038/sj.gt.3302999   (Journal Full-text)

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 microvessel 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.




  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
KDRHumanrenal cell carcinoma  ISOKdr (Mus musculus) RGD 
KdrRatrenal cell carcinoma  ISOKdr (Mus musculus) RGD 
KdrMouserenal cell carcinoma  IMP  RGD 


Genes (Rattus norvegicus)
Kdr  (kinase insert domain receptor)

Genes (Mus musculus)
Kdr  (kinase insert domain protein receptor)

Genes (Homo sapiens)
KDR  (kinase insert domain receptor)