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

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.

• Authors: Mitomu Kioi, Takeshi Shimamura, Hideyuki Nakashima, Makoto Hirota, Iwai Tohnai, Syed R Husain, Raj K Puri
• Journal: International journal of cancer (Int J Cancer) Vol. 124 Issue 6 Pg. 1440-8 (Mar 15 2009) ISSN: 1097-0215 [Electronic] United States
• PMID: 19065664 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents, Phytogenic
• Exotoxins
• IL13-PE38
• Interleukin-13
• Recombinant Fusion Proteins
• Paclitaxel

Topics

• Animals
• Antineoplastic Agents, Phytogenic (therapeutic use)
• Carcinoma, Squamous Cell (drug therapy, genetics)
• Cell Line, Tumor
• Disease Models, Animal
• Drug Synergism
• Exotoxins (therapeutic use)
• Humans
• Interleukin-13 (therapeutic use)
• Mice
• Mouth Neoplasms (drug therapy, genetics)
• Paclitaxel (therapeutic use)
• Recombinant Fusion Proteins (therapeutic use)
• Reverse Transcriptase Polymerase Chain Reaction
• Tongue Neoplasms (drug therapy)
• Transplantation, Heterologous