Suppression of TGF-beta 1 in human gliomas by retroviral gene transfectionenhances susceptibility to LAK cells

Human glioma cell line, Onda 10 produces TGF-beta 1. TGF-beta 1 has a biolo gical role for the immunosuppression of the host. We have investigated whet her suppression of TGF-beta 1 on human glioma cell enhanced the susceptibil ity to lymphokine-activated killer (LAK) cells. In vitro, susceptibility to LAK cells on Onda 10 cell is augmented by retroviral gene transfection wit h antisense TGF-beta 1. Nude mice bearing Onda 10 cells transduced with ant isense TGF-beta 1 gene has a longer life span compared to mice carrying tha t of sense TGF-beta 1 gene or vector alone. The cytotoxic activity of LAK c ells induced from spleen cells of mice carrying antisense TGF-beta 1 gene t ransduced cells is higher against Onda 10 cell than that of LAK cells from mice carrying vector alone transduced cells. Also, antisense TGF-beta 1 gen e 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-beta 1 gene transduced cells and that the increased systemic immunity could be ascribed to the increased immunogenicity of the tumor cells. The gene therapy for m alignant glioma with antisense TGF-beta 1 gene is expected to be promising.