Source: Annual Congress 2002 - Lung cancer biology

Abstract

Adenoviral vectors are the most important vehicles for gene therapy trials in lung cancer. First-generation adenoviral vectors are known to cause immune reactions and cell cycle disturbances due to expression of viral proteins. New [dsquote]high-capacity[dsquote] (hc) vectors have all viral coding sequences removed to reduce these reactions in the host organism.
In our study we compared a first-generation with two hc-vectors (GS47 and FK7) with regard to cell damage, induction of apoptosis and cell cycle disorder in vitro. Cellular damage was detected in hepatocytes measuring LDH, GOT and GPT. Annexin V and propidium iodide stainings of colorectal cancer cells (LoVo) were used for analysis of apoptotic changes. In the same cells we performed flow cytometric cell cycle analysis.
Higher levels of LDH, GOT and GPT were found after transfection with first-generation vectors vs. hc-vectors indicating cellular damage. Apoptotic changes were detected after first-generation but not after hc-vector transfection comparing with controls. These differences were also found on the cell cycle level. Cells accumulated in G2/M-phase after first-generation vector while cell cycle distribution was identical after hc-vector and buffer.
Our results suggest that high capacity vectors have advantages over first-generation vectors in terms of toxicity and interference with the host cell.

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U. Liebers, B. Schmidt, S. Kochanek, A. Schumacher, G. Wolff, C. Witt (Berlin, Cologne, Germany). High-capacity adenoviral vectors for gene transfer: reduced toxicity and reduced cell-cycle dysregulation. Eur Respir J 2002; 20: Suppl. 38, 225

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