Intratumoral injection of dendritic and irradiated glioma cells induces anti-tumor effects in a mouse brain tumor model.
Malignant astrocytoma is the most common primary brain tumor in adults. The median survival of patients with malignant astrocytomas (high-grade astrocytomas) is about 1-2 years, despite aggressive treatment that includes surgical resection, radiotherapy and cytotoxic chemotherapy. Therefore, novel therapeutic approaches are needed to prolong survival. We investigated antitumor immunity conferred by the intratumoral injection of dendritic (DC) and irradiated glioma cells (IR-GC) in a mouse brain tumor model. Intratumorally injected DC migrated to the lymph nodes and elicited systemic immunity against autologous glioma cells. In a treatment model, intratumoral injection of DC and IR-GC prolonged the survival of brain tumor-bearing mice. Efficacy was reduced when studies were performed in mice depleted of CD8(+) T cells. Administration of DC or IR-GC alone had no effect on survival of brain tumor-bearing mice. CTL activity against glioma cells from immunized mice was also stimulated by coadministration of DC and IR-GC compared with the controls. These results support the therapeutic efficacy of intratumoral injection of DC and IR-GC.
Department of Neurosurgery, Institute of DNA Medicine, Jikei University, Tokyo, Japan, tkikuchi@jikei.ac.jp
Tetsuro
T
Kikuchi
Yasuharu
Y
Akasaki
Toshiaki
T
Abe
Tsuneya
T
Ohno
D000818:Animals; D001254:Astrocytoma / Q000628:therapy; D001932:Brain Neoplasms / Q000628:therapy*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002465:Cell Movement; D003712:Dendrites / Q000276:immunology* / Q000378:metabolism; D005910:Glioma / Q000276:immunology* / Q000378:metabolism; D007167:Immunotherapy / Q000379:methods*; D007694:Killer Cells, Natural / Q000166:cytology; D008198:Lymph Nodes / Q000378:metabolism; D051379:Mice; D013997:Time Factors; D014407:Tumor Cells, Cultured