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

Original Article

Journal of Korean Neurosurgical Society 2005;38(2): 126-131.

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

Department of Neurosurgery, Our Lady of Mercy Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea. dschung@olmh.cuk.ac.kr

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.

Key Words: Dendritic cell; Interferon-gamma; Tumor-specific cytotoxicity; Glioma apoptotic body; Glioma cell lysate