IL-13 cytotoxin has potent antitumor activity and synergizes with paclitaxel in a mouse model of oral squamous cell carcinoma

Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
International Journal of Cancer (Impact Factor: 5.01). 03/2009; 124(6):1440-8. DOI: 10.1002/ijc.24067
Source: PubMed

ABSTRACT Interleukin-13 receptor-targeted cytotoxin (IL13-PE38) is highly cytotoxic to certain types of human cancers expressing abundant levels of IL-13Ralpha2 chain. Although IL13-PE38 is being tested in a Phase III clinical trial in brain tumors, the activity of IL13-PE38 alone or when combined with taxane, a chemotherapeutic drug for oral squamous cell carcinoma (OSCC), has not been investigated. Here, we show that approximately 40% of OSCCs (n = 50) in a tissue array are strongly positive for IL-13Ralpha2, whereas normal oral mucosa (n = 10) expresses very low or undetectable levels evaluated by immunohistochemistry. IL13-PE38 was highly cytotoxic to OSCC cell lines, but not cytotoxic to normal oral fibroblasts. IL13-PE38 mediated a synergistic antitumor effect with paclitaxel in OSC-19 in vitro and in vivo in the orthotopic OSCC tongue tumor model. Real-time tumor growth was monitored by optical imaging using a Xenogen-IVIS imaging system. Treated animals showed significant (p < 0.05) improvement in survival, which correlated with in vivo imaging of tumor response without evidence of visible toxicity. Gene transfer of IL-13Ralpha2 in oral cancer cells increased sensitivity of OSCC cell line to IL13-PE38 in vitro. Retrovirus-mediated gene-transfer of IL-13Ralpha2 in HSC-3 into tongue tumors in vivo dramatically enhanced the antitumor activity of IL13-PE38, providing complete elimination of established tumors and prolonging survival of these animals. These results indicate that IL13-PE38 in combination with paclitaxel acting via different mechanisms may be a potential treatment option for IL-13Ralpha2 expressing OSCC or for the treatment of non-IL-13Ralpha2 expressing OSCC combined with gene transfer of IL-13Ralpha2.

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