Bone marrow-derived dendritic cells pulsed with tumor homogenate induce immunity against syngeneic intracerebral glioma

To evaluate the efficacy and toxicity of dendritic cell (DC) based therapy for intracerebral gliomas, we utilized a cell Line derived from an astrocyt oma that arose spontaneously in a VM/Dk mouse. This astrocytoma mirrors hum an gliomas phenotypically, morphologically and secretes transforming growth factor (TGF)-beta s, immunosuppressive cytokines secreted by human gliomas . Systemic vaccination of mice with DCs pulsed with tumor homogenate follow ed by intracranial tumor challenge produced a > 160% increase in median sur vival (p = 0.016) compared with mice vaccinated with PBS or unpulsed DCs (p = 0.083). Fifty percent of mice treated with pulsed DCs survived long-term . Immunologic memory was demonstrated by survival of mice rechallenged with tumor. Both cell-mediated and humoral immunity was induced. On histologica l examination only focal areas of demyelination at the tumor implantation s ite were present. There was no evidence that autoimmune encephalomyelitis w as induced by DC vaccination. Therefore, in a murine model, vaccination wit h DCs pulsed with glioma tumor homogenate is a safe and effective therapy a gainst a syngeneic glioma located in the immunologically privileged central nervous system (CNS). (C) 2000 Elsevier Science B.V. All rights reserved.