Gene therapy for experimental brain tumors using a xenogenic cell line engineered to secrete hIL-2.
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.
Lesniak
Maciej S
MS
Department of Neurosurgery, The Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA.
Tyler
Betty M
BM
Pardoll
Drew M
DM
Brem
Henry
H
D000818:Animals; D000917:Antibody Formation; D001932:Brain Neoplasms / Q000503:physiopathology / Q000628:therapy*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D017690:Cell Transplantation; D004727:Endothelium / Q000166:cytology / Q000378:metabolism; D015316:Genetic Therapy; D006801:Humans; D007167:Immunotherapy; D007267:Injections; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism*; D008545:Melanoma / Q000503:physiopathology / Q000628:therapy*; D051379:Mice; D051381:Rats; D016019:Survival Analysis; D014183:Transplantation, Heterologous
D007376:Interleukin-2