Novel strategies to augment genetically delivered immunotoxin molecular therapy for c

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1: Cancer Gene Ther. 2009 May 22. [Epub ahead of print] Links

Novel strategies to augment genetically delivered immunotoxin molecular therapy for cancer therapy.

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]