Cytotoxicities of Tumor-specific T Lymphocytes Primed by Glioma Apoptotic Body-or Glioma Cell Lysate-pulsed Dendritic Cells

Kim, Jong Tae; Chung, Dong Sup; Kwak, Seung Won; Han, Young Min; Park, Young Sup; Kim, Moon Chan

Abstract

OBJECTIVE
The choice of tumor antigen for dendritic cell(DC)-loading has still been an unresolved problem in the DC-based vaccine strategies against malignant gliomas that has not been found well-characterized tumor specific antigens. In this study, we compare tumor-specific T cell response induced by glioma apoptotic body(GAB)-pulsed DCs to response induced by glioma cell lysate-pulsed ones quantitatively. METHODS: DCs generated in the presence of granulocyte macrophage-colony stimulating factor and interleukin(IL)-4 from peripheral blood mononuclear cells(PBMCs) of HLA-A2 positive healthy donors were cultured. Each GABs and glioma cell lysate generated from HLA-A2 positive T98G glioblastoma cells were co-incubated with DCs. CD8+ T lymphocytes isolated from PBMCs of same donors were cultured in media containing IL-2 and either stimulated by GAB- or lysate-pulsed DCs three times at a weekly interval. The interferon(IFN)-gamma concentrations of each cell culture supernate were measured by enzyme immunoassay technique. Cytolytic activity of the generated cytotoxic CD8+ T cells either stimulated with GAB- or lysate-pulsed DCs was determined by a standard 4-h 51Cr-release assay. RESULTS: IFN-gamma production and cytolytic activity of effector T cells stimulated by GAB-pulsed DCs were significantly higher than those of T cells stimulated by lysate-pulsed ones. CONCLUSION: These results indicate the choice of antigen is a critical determinant in the induction of antitumor immunity against malignant glioma. Antigen preparations from GABs represent a promising alternative to glioma cell lysate in DC-based glioma vaccine strategies.