Abstract 1794: A novel combination therapeutic approach for targeting murine cancers with IL-13 receptor alpha 2 DNA vaccine and an immunotoxin

Abstract

Abstract Iinterleukin-13 receptor α2 (IL-13Rα2), a cancer testis antigen, is frequently over-expressed on human solid tumors and can be effectively targeted by a recombinant fusion immunotoxin composed of IL-13 and a mutated form of Pseudomonas exotoxin (IL13-PE). We have previously demonstrated that cDNA vaccine to IL-13Rα2 or IL13-PE alone can cause regression of established murine cancer. Here, we demonstrate that combination therapy with DNA vaccine and IL13-PE can cause a remarkable antitumor effect in advanced tumor metastasis models induced by 4T1 breast carcinoma and MCA304 sarcoma. Murine metastatic tumor models were developed by i.v. injection of either 1×105 4T1 or 1×106 MCA304 cells. Mice with established 4T1 metastasis received twice daily i.p. injections of IL13-PE (50 ug/kg/injection) on five consecutive days beginning day 7 followed by i.m. DNA vaccination (100 μg/day) on day 18, 23, 28 and 33. The combination therapy significantly (p<0.01) prolonged overall survival (56 days) of animals compared to control (32 days), IL-13PE alone (43 days) or DNA vaccine alone (40 days). Similar results were observed in MCA304 sarcoma tumor model. Mice treated with combination therapy showed higher CTL activity and IFN-γ release from splenocytes in vitro compared to the controls in both tumor models. Immunofluorescence analyses exhibited infiltration of CD4+ and CD8+ T cells in lung tissues of immunized mice. The role of CD4+ and CD8+ T cells in tumor immunity was further confirmed by similar treatment of tumor-bearing RAG2 KO mice (deficient in T and B cells), which showed no response to therapy. Interestingly, tumor bearing mice treated with combination therapy recruited much lower number of myeloid-derived suppressor cells (MDSC) in lungs than PBS treated controls. These results indicate that combination therapy with IL13-PE followed by DNA vaccine may be a new therapeutic approach of treating human cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1794. doi:10.1158/1538-7445.AM2011-1794