Gene therapy for experimental brain tumors using a xenogenic cell line engineered to secrete hIL-2.

Abstract

Local delivery of cytokines has been shown to have a potent anti-tumor activity against a wide range of malignant brain tumors. In this study, we examined the feasibility and efficacy of using a rat endothelial cell line (NTC-121) transfected with the human interleukin-2 (IL-2) gene in treating experimental murine CNS tumors. The NTC-121 cells were injected intracranially in C57BL/6 mice (N = 10/group) along with non-irradiated, non-transfected B16/F10 (wild type) melanoma cells. Sixty percent of mice treated with IL-2 (p < 0.001 vs. control) were long-term survivors (LTS) of > 120 days. Control animals that received only wild type cells had a median survival of 18 days (range 15-20). Histopathological examination of brains from animals sacrificed at different times showed no tumor growth in the non-irradiated NTC-121 group, moderate (1-2 mm) tumor growth in the irradiated group, and gross tumor invasion (>2 mm) and tissue necrosis in the control group. Moreover, animals treated with IL-2 showed an accumulation of CD8+ T cells around the site of the injected tumor. The use of a xenogenic cell line to deliver hIL-2 stimulates a strong immunologic cytotoxic anti-tumor response that leads to significant prolongation of survival in mice challenged with the B16/F10 intracranial melanoma tumor. Our findings demonstrate that the use of a xenogenic cell line can provide a potent vehicle for the delivery of gene therapy and may therefore represent a new approach for brain tumor therapy.