RGD Reference Report - Adenovirus-mediated interleukin 3 beta gene transfer by isolated limb perfusion inhibits growth of limb sarcoma in rats. - Rat Genome Database

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Adenovirus-mediated interleukin 3 beta gene transfer by isolated limb perfusion inhibits growth of limb sarcoma in rats.

Authors: De Wilt, JH  Bout, A  Eggermont, AM  Van Tiel, ST  De Vries, MW  Ten Hagen, TL  De Roos, WK  Valerio, D  Van der Kaaden, ME 
Citation: de Wilt JH, etal., Hum Gene Ther. 2001 Mar 20;12(5):489-502.
RGD ID: 2317666
Pubmed: PMID:11268282   (View Abstract at PubMed)
DOI: DOI:10.1089/104303401300042384   (Journal Full-text)

Cytokine gene transfer using (multiple) intratumoral injections can induce tumor regression in several animal models, but this administration technique limits the use for human gene therapy. In the present studies we describe tumor growth inhibition of established limb sarcomas after a single isolated limb perfusion (ILP) with recombinant adenoviral vectors harboring the rat IL-3 beta gene (IG.Ad.CMV.rIL-3 beta). In contrast, a single intratumoral injection or intravenous administration did not affect tumor growth. Dose-finding studies demonstrated a dose-dependent response with a loss of antitumor effect below 1 x 10(9) IU of IG.Ad.CMV.rIL-3 beta. Perfusions with adenoviral vectors bearing a weaker promoter (MLP promoter) driving the rIL-3 beta gene did not result in antitumor responses, suggesting that the rIL-3 beta-mediated antitumor effect depends on the amount of rIL-3 beta protein expressed by the infected cells. Furthermore, it was shown by direct comparison that ILP with IG.Ad.CMV.rIL-3 beta in the ROS-1 osteosarcoma model is at least as efficient as the established therapy with the combination of TNF-alpha and melphalan. Treatment with IG.Ad.CMV.rIL-3 beta induced a transient dose-dependent leukocytosis accompanied by an increase in peripheral blood levels of histamine. Leukocyte infiltrations were also histopathologically demonstrated in tumors after perfusion. These results demonstrate that ILP with recombinant adenoviral vectors carrying the IL-3 beta transgene inhibits tumor growth in rats and suggest that cytokine gene therapy using this administration technique might be beneficial for clinical cancer treatment.




  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
IL3Humanosteosarcoma  ISOIl3 (Rattus norvegicus) RGD 
Il3Ratosteosarcoma  IMP  RGD 
Il3Mouseosteosarcoma  ISOIl3 (Rattus norvegicus) RGD 


Genes (Rattus norvegicus)
Il3  (interleukin 3)

Genes (Mus musculus)
Il3  (interleukin 3)

Genes (Homo sapiens)
IL3  (interleukin 3)