Immunization with dendritic cells pulsed with tumor extract increases survival of mice bearing intracranial gliomas

The purpose of this study is to investigate the efficacy of dendritic cell- mediated immunotherapy against intracranial gliomas. Cloned DC2.4 dendritic cells originating from C57BL/6 mice were pulsed with glioma GL261 cell ext racts and administered i.p. to C57BL/6 mice with intracranial GL261 gliomas . The survival of mice with and without pulsed dendritic cells was monitore d after intracranial implantation of the GL261 glioma cells. Fluorescence a ctivated cell sorting (FACS) analysis showed that DC2.4 cells express high levels of MHC class I and class II molecules, costimulatory molecules B7-1 and B7-2, and the cell adhesion molecule ICAM-1. Antigen-presenting capabil ities in these dendritic cells were initially characterized in vitro by a m ixed lymphocyte reaction, showing that Balb/c CD4(+) and CD8(+) T cells wer e able to generate allogeneic responses to DC2.4 cells. Tumor extract-pulse d DC2.4 dendritic cells were then used for the treatment of C57BL/6 mice wi th syngeneic GL261 gliomas. Animals with intracranial GL261 gliomas and vac cinated i.p. with pulsed DC2.4 dendritic cells exhibited significantly enha nced survival, relative to animals treated with saline or non-pulsed DC2.4 cells alone. In addition, cured animals showed an increased delayed-type hy persensitivity response to GL261 cells and survived when rechallenged with intracranial GL261 gliomas. In summary these results indicate that dendriti c cells pulsed with tumor extract can enhance immune responses to tumor ant igen and therefore represent a potential immunotherapeutic approach for tre ating patients with intracranial gliomas.