Novel strategies to augment genetically delivered immunotoxin molecular therapy for c
 

<dl class="AbstractPlusReport"><dt class="head">1: Cancer Gene Ther. 2009 May 22. [Epub ahead of print]http://www.ncbi.nlm.nih.gov/corehtml...ges-lo_npg.gif <script language="JavaScript1.2"><!-- var Menu19461676 = [ ["UseLocalConfig", "jsmenu3Config", "", ""], ["LinkOut", "window.top.location='/sites/entrez?Cmd=ShowLinkOut&Db=pubmed&TermToSearch=1946 1676&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubm ed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubme d_RVAbstractPlus' ", "", ""] ] --></script>Links
</dt><dd class="abstract"> Novel strategies to augment genetically delivered immunotoxin molecular therapy for cancer therapy.

<!--AuthorList-->Liu X, Wu J, Zhang S, Li C, Huang Q.
Experimental Center, First People's Hospital, Shanghai Jiaotong University, Shanghai, China.
Immunotoxin therapy is a promising molecular cancer treatment strategy. Its main advantage is seletive cytotoxicity towards tumor cells and minimal toxicity in normal tissues. However, a short half-life and rapid clearance severely hampers its clinical application. We report here a novel genetic approach in which a recombinant adenovirus vector was used to deliver an immunotoxin gene e23(scFv)-PE40 targeted to the oncogene c-erbB-2 (also known as Her2/neu). This vector, when combined with a low dose of a conditionally replicative adenovirus vector (CRAd), has enhanced tumor-killing ability either alone or in combination with the chemotherapeutic agent etoposide. Our data show that low-dose CRAd facilitated the replication of replication-deficient Ad-e23(scFv)-PE40 up to 6-20 times and the transcription of e23(scFv)-PE40 gene up to 12 times. Moreover, etoposide increased the e23(scFv)-PE40 transcription up to 8.5 times. Furthermore, we show that systemic application of Ad-e23(scFv)-PE40 and enhanced expression of the immunotoxin gene was well tolerated as determined by serum biochemical markers and histological examination of most vital organs. Taken together, our data support a novel genetic immunotoxin delivery approach that may yield enhanced efficacy against a variety of Her2/neu-expressing tumors.Cancer Gene Therapy advance online publication, 22 May 2009; doi:10.1038/cgt.2009.30.
PMID: 19461676 [PubMed - as supplied by publisher]
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