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 astrocytoma that arose spontaneously in a VM/Dk mouse. This astrocytoma mirrors human gliomas phenotypically, morphologically and secretes transforming growth factor (TGF)-betas, immunosuppressive cytokines secreted by human gliomas. Systemic vaccination of mice with DCs pulsed with tumor homogenate followed by intracranial tumor challenge produced a > 160% increase in median survival (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 histological examination only focal areas of demyelination at the tumor implantation site were present. There was no evidence that autoimmune encephalomyelitis was induced by DC vaccination. Therefore, in a murine model, vaccination with DCs pulsed with glioma tumor homogenate is a safe and effective therapy against a syngeneic glioma located in the immunologically privileged central nervous system (CNS).
Heimberger
A B
AB
Division of Neurosurgery, Duke University Medical Center, Durham, NC 27710, USA.
Crotty
L E
LE
Archer
G E
GE
McLendon
R E
RE
Friedman
A
A
Dranoff
G
G
Bigner
D D
DD
Sampson
J H
JH
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology*; D001932:Brain Neoplasms / Q000276:immunology* / Q000628:therapy; D003713:Dendritic Cells / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000517:prevention & control; D005910:Glioma / Q000276:immunology* / Q000628:therapy; D051379:Mice; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured; D014611:Vaccination