Details

Autor(en) / Beteiligte

• Rohr, Ulrich-Peter
• Wulf, Marc-Andre
• Stahn, Susanne
• Heyd, Florian
• Steidl, Ulrich
• Fenk, Roland
• Opalka, Bertram
• Pitschke, Gerald
• Prisack, Hans-Bernd
• Bojar, Hans
• Haas, Rainer
• Kronenwett, Ralf

Titel

Non-small lung cancer cells are prime targets for p53 gene transfer mediated by a recombinant adeno-associated virus type-2 vector

Ist Teil von

• Cancer gene therapy, 2003-12, Vol.10 (12), p.898-906

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2003

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• In this study, we elucidated the potential of recombinant adeno-associated virus type-2 (rAAV-2) vectors for lung cancer gene therapy. Cell lines of the three major histological subtypes of non-small cell lung cancer (NSCLC) were highly susceptible for rAAV-2 showing transduction rates between 63.4 and 98.9%. In contrast, cell lines of small cell carcinomas were resistant to rAAV-2 infection. For restoration of p53 function in p53 deficient NSCLC, a rAAV-2 vector was constructed containing wt p53 cDNA. Following transduction with rAAV-p53, cell growth of all NSCLC cell lines was significantly reduced in a dose-dependent manner between 44 and 71.7% in comparison with rAAV-GFP transduced cells. The reduction of tumor cell growth was associated with increased apoptosis. Adding cisplatin to rAAV-p53-infected cells led to a significant growth inhibition between 81 and 91% indicating a synergistic effect between cisplatin and rAAV-p53. Interestingly, the tumor cells surviving cisplatin and rAAV-p53 treatment were inhibited in their ability to form colonies as reflected by a reduction of colony growth between 57 and 90.4%. In conclusion, rAAV-2 vectors exhibit a strong tropism for NSCLC. Successful inhibition of tumor cell growth following transduction with a rAAV-p53 vector underlines the potential role of rAAV-2 in cancer gene therapy.