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.

M2-polarized macrophages contribute to neovasculogenesis, leading to relapse of oral cancer following radiation

“…IL-13Rα2, one of the IL-13 receptors, is highly expressed in some cancer cells, including GBM23 and OSCC24; therefore, targeting this receptor, such as CAR-T and IL13-PE, would be new strategy for these cancer patients25. Interestingly, recent reports have shown that macrophages recruited by inflammation in ulcerative colitis and pulmonary fibrosis also express IL-13Rα22627.…”

A Novel Combination Immunotherapy for Cancer by IL-13Rα2–Targeted DNA Vaccine and Immunotoxin in Murine Tumor Models

“…We also showed that IL13-PE combined with paclitaxel mediated potent antitumor effects in vitro and in vivo in a mouse tumor model of human oral squamous cell carcinoma (40) and, combined with gemcitabine, it mediated synergistic antitumor effects and prolonged the survival of animals in a pancreatic cancer model (41). In this study, we showed that IL13-PE may act as a strong immune stimulant and synergize with IL-13Rα2 DNA vaccine in inhibiting tumor growth and prolonging the survival of animals with established breast cancer or sarcoma tumors.…”

Nanotechnology-based drug delivery systems for treatment of oral cancer: a review

“…178 Hosmer et al in 2012, studied mesophase lamellar LCs formed with glycerides for the incorporation of the anticancer drug paclitaxel. 184 Paclitaxel is highly effective against various types of cancer, including oral cancer; [185][186][187] however, it has severe adverse effects associated with systemic drug administration, including hypersensitivity reactions, thrombocytopenia, and neutropenia. 188,189 Hosmer et al 184 found that, among the formulations studied, the Brij-based lamellar phase containing 20% medium-chain …”