The generation of anti-tumoral cells using dentritic cells from the peripheral bloood of patients with malignant brain tumors.
Dendritic cells (DCs) can be the principal initiators of antigen-specific immune responses. We analyzed the in vitro-responses against brain tumor cells using DCs from the peripheral blood of patients with brain tumors. Peripheral blood mononuclear cells (PBMC) were obtained from 19 patients with malignant brain tumors: 12 metastatic brain tumors of lung adenocarcinoma, 7 high-grade astrocytomas. PBMC were cultured with 100 ng/ml of GM-CSF and 10 ng/ml of IL-4 for 5 7 days in order to produce mature DCs. The autologous tumor lysate (5 mg/ml, containing 1 x 10(6) cells) was then added to the cultured DCs. Using the DCs generated by these treatments, we assessed the changes that occurred in their immune responses against brain tumor via 51Cr-release and lymphocyte proliferation assays. We found that the matured DCs displayed the typical surface phenotype of CD3+, CD45+, CD80+ and CD86+. After the pulsation treatment with tumor lysate, DCs were found to have strong cytotoxic T lymphocyte activity, showing 42.5+12.7% killing of autologous tumor cells. We also found an enhancement of allogeneic T cell proliferation after pulsing the DC with tumor lysate. These data support the efficacy of DC-based immunotherapy for patients with malignant brain tumors.
Yoshida
S
S
Department of Neurosurgery, Niigata Cancer Center Hospital,  Japan. brain@niigata-cc.niigata.niigata.jp
Morii
K
K
Watanabe
M
M
Saito
T
T
Yamamoto
K
K
Tanaka
R
R
D000230:Adenocarcinoma / Q000097:blood / Q000276:immunology* / Q000556:secondary; D001254:Astrocytoma / Q000097:blood / Q000276:immunology*; D001932:Brain Neoplasms / Q000097:blood / Q000276:immunology* / Q000556:secondary; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D016219:Immunotherapy, Adoptive; D015847:Interleukin-4 / Q000494:pharmacology; D008175:Lung Neoplasms / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor