Adenovirus mediated gene therapy in a glioblastoma vaccine model; specificantitumor immunity and abrogation of immunosuppression

Clinical trials are being performed using tumor genetically engineered to p roduce cytokines as a vaccine. The design of such a vaccine may be made mor e effective by further study using in-vitro as well as in-vivo models. We s tudied an in-vitro tumor 'vaccine' model in glioblastoma. We have demonstra ted high efficiency transfection of the Interleukin-2 (IL-2) gene into glio blastoma cell lines using adenoviral vectors. Glioblastoma cell lines trans duced with this vector could produce high levels of IL-2 for up to 2 weeks, long enough to elicit an antitumor immune response. We studied tumor/effec tor cell interactions using cytotoxicity assays coupled with flow cytometri c analysis. Activation of CD8+ and expansion of CD3 + /CD16+ effector cell subpopulations were observed, suggesting the generation of a specific anti- tumor response and the potential for systemic immunity. We demonstrated tha t glioblastoma produce immunosuppressive factors which reduce the antitumor response by peripheral blood effector cells. These immunosuppressive facto rs could be neutralized to improve antitumor response. A better understandi ng of tumor/effector cell interactions may improve the design of gene thera py trials.