Suppression of TGF-beta1 in human gliomas by retroviral gene transfection enhances susceptibility to LAK cells.

Abstract

Human glioma cell line, Onda 10 produces TGF-beta1. TGF-beta1 has a biological role for the immunosuppression of the host. We have investigated whether suppression of TGF-beta1 on human glioma cell enhanced the susceptibility to lymphokine-activated killer (LAK) cells. In vitro, susceptibility to LAK cells on Onda 10 cell is augmented by retroviral gene transfection with antisense TGF-beta1. Nude mice bearing Onda 10 cells transduced with antisense TGF-beta1 gene has a longer life span compared to mice carrying that of sense TGF-beta1 gene or vector alone. The cytotoxic activity of LAK cells induced from spleen cells of mice carrying antisense TGF-beta1 gene transduced cells is higher against Onda 10 cell than that of LAK cells from mice carrying vector alone transduced cells. Also, antisense TGF-beta1 gene transduced cells are much more sensitive to LAK cells compared to Onda 10. These suggest that the augmented host systemic immunity in mice is one of the mechanisms of the reduced tumorigenicity of antisense TGF-beta1 gene transduced cells and that the increased systemic immunity could be ascribed to the increased immunogenicity of the tumor cells. The gene therapy for malignant glioma with antisense TGF-beta1 gene is expected to be promising.