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Induction of cytotoxic T lymphocytes against human cancer cell lines using dendritic cell-tumor cell hybrids generated by a newly developed electrofusion technique.
Imura, Kenichiro; Ueda, Yuji; Hayashi, Takashi; Itoh, Tsuyoshi; Shimizu, Keiji; Tamai, Hidemasa; Yano, Yutaro; Naito, Kei; Kohara, Junji; Nakane, Kazuki; Matsuura, Yuko; Takeda, Atsuko; Takeda, Takahisa; Kawai, Keiichi; Yamagishi, Hisakazu.
Afiliação
  • Imura K; Department of Surgery, Division of Digestive Surgery, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kyoto 602-8566, Japan.
Int J Oncol ; 29(3): 531-9, 2006 Sep.
Article em En | MEDLINE | ID: mdl-16865268
Recently, dendritic cells (DCs) and DC-tumor cell hybrids (DC-tumor hybrids) have been used for cancer vaccine therapy in a clinical trial. DC-tumor hybrids combine the potent antigen-presenting capacity of DCs with the ability to present all tumor antigens expressed on tumor cells to T cells. We used DC-tumor hybrids as stimulator cells to induce tumor-specific cytotoxic T lymphocytes (CTLs) in vitro. DC-tumor hybrids were generated from human monocyte-derived DCs and human cancer-cell lines (GT3TKB, lung cancer; GCIY, gastric cancer) by our newly developed electrofusion technique, established and refined with the use of mouse cells. To evaluate the capacity of DC-tumor hybrids generated by our method to induce tumor antigen-specific CTLs, we performed a cytotoxic assay and an interferon-gamma release assay using CD8-dominant effector lymphocytes induced by them. DC-tumor hybrids more effectively induced tumor-specific primary T-cell response than did stimulation with DCs co-cultured with irradiated tumor cells overnight, irradiated tumor cells alone, or a mixture of DCs and irradiated tumor cells. DC-tumor hybrids were generated at a high fusion rate by our electrofusion technique. When CTLs were induced by DC-tumor hybrids in vitro, the high fusion rate did not contribute to the induction of CTLs with increased tumor-specific cytotoxicity. The addition of interleukin-12 to the culture medium did not augment the cytotoxicity of CTLs. Overall, our results suggest that DC-tumor hybrids effectively induce human tumor-specific CTLs and may thus be applicable for clinical trials of adoptive immunotherapy.
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Gástricas / Células Dendríticas / Linfócitos T Citotóxicos / Neoplasias Pulmonares / Antígenos de Neoplasias Limite: Adult / Humans / Male Idioma: En Ano de publicação: 2006 Tipo de documento: Article
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Gástricas / Células Dendríticas / Linfócitos T Citotóxicos / Neoplasias Pulmonares / Antígenos de Neoplasias Limite: Adult / Humans / Male Idioma: En Ano de publicação: 2006 Tipo de documento: Article