Adenoviral vector–mediated gene transfer of IL-13Rα2 chain followed by IL-13 cytotoxin treatment offers potent targeted therapy for cytotoxin-resistant cancers
✍ Scribed by Makoto Saito; Takashi Murata; Ken Watanabe; Koji Kawakami; Motoyoshi Suzuki; Takehiko Koji; Raj K. Puri; Kaio Kitazato; Nobuyuki Kobayashi
- Book ID
- 102271610
- Publisher
- John Wiley and Sons
- Year
- 2005
- Tongue
- French
- Weight
- 404 KB
- Volume
- 116
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Abstract
Previous studies demonstrated that IL‐13Rα2 chain–overexpressing cancer cells were highly sensitive to IL‐13 cytotoxin (IL13‐PE38QQR) and could be targeted by cytotoxin treatment. However, the majority of human tumors do not express high levels of IL‐13Rα2 chain. To expand the IL‐13 cytotoxin–mediated cancer targeting therapy, we combined cytotoxin treatment with gene transfer of IL‐13Rα2 chain. We constructed a recombinant adenoviral vector carrying the human IL‐13Rα2 gene (Ad‐IL‐13Rα2), which expresses high levels of IL‐13Rα2 chain on infected cells. Human cancer cell lines A549 and HOS, which originally show no IL‐13Rα2 expression and little sensitivity to IL‐13 cytotoxin, were effectively converted to become sensitive to this cytotoxin after Ad‐IL‐13Rα2 infection. The CC~50~ of IL‐13 cytotoxin for Ad‐IL‐13Rα2‐infected A549 cells was <10 ng/ml, whereas the CC~50~ for uninfected or control vector‐infected cells was >500 ng/ml. We also examined the antitumor activity of IL‐13 cytotoxin in an established xenograft model of cytotoxin‐resistant human lung tumor. Only a single i.t. injection of Ad‐IL‐13Rα2 markedly enhanced the sensitivity of established tumors to IL‐13 cytotoxin treatment; furthermore, this antitumor effect was significantly sustained for more than 1 month after the last treatment with IL‐13 cytotoxin. Taken together, these results suggest the combination of adenoviral vector–mediated IL‐13Rα2 gene transfer and IL‐13 cytotoxin administration can be an effective targeting approach for several types of IL‐13 cytotoxin–resistant cancers which show no or little expression of IL‐13Rα2 chain. © 2005 Wiley‐Liss, Inc.