Combination therapy by IL-13 receptor alpha2 DNA vaccine and immunotoxin inhibits metastatic murine cancers

Monday, October 24, 2011 — Poster Session I
Noon – 2:00 p.m.	Natcher Conference Center	FDA/CBER	CANCER-16

Authors

• H Nakashima
• BH Joshi
• SR Husain
• RK Puri

Abstract

Interleukin-13 receptor alpha2 is frequently over-expressed on human solid tumors and can be targeted by a recombinant fusion immunotoxin composed of IL-13 and a mutated Pseudomonas exotoxin (IL13-PE). Here, we demonstrate that combination therapy with IL-13Ralpha2 DNA vaccine and IL13-PE can inhibit metastasis in two murine tumor models. Metastatic tumor models were developed by i.v. injection of either 1x10^5 4T1 breast or 1x10^6 MCA304 sarcoma 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 ug/day) on day 18, 23, 28 and 33. The combination therapy significantly prolonged survival of animals compared to the control. IL-13PE alone or DNA vaccine alone. MCA304 model gave similar results. Mice treated with combination therapy showed higher CTL activity and IFN-gamma release from splenocytes in vitro compared to the controls in both models. Immunofluorescence analyses exhibited infiltration of CD4+ and CD8+ T cells in lung tissues of immunized mice. Interestingly, these mice recruited much lower number of myeloid-derived suppressor cells and tumor associated macrophages in lungs than PBS treated controls. These results indicate that this combination therapy may also inhibit metastasis in human cancer.

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