Induction of cytotoxic T lymphocytes against human cancer cell lines using dendritic cell-tumor cell hybrids generated by a newly developed electrofusion technique.
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.
Imura
Kenichiro
K
Department of Surgery, Division of Digestive Surgery, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kyoto 602-8566, Japan.
Ueda
Yuji
Y
Hayashi
Takashi
T
Itoh
Tsuyoshi
T
Shimizu
Keiji
K
Tamai
Hidemasa
H
Yano
Yutaro
Y
Naito
Kei
K
Kohara
Junji
J
Nakane
Kazuki
K
Matsuura
Yuko
Y
Takeda
Atsuko
A
Takeda
Takahisa
T
Kawai
Keiichi
K
Yamagishi
Hisakazu
H
D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology; D000328:Adult; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000473:pathology; D002459:Cell Fusion; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D006822:Hybrid Cells / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000494:pharmacology; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology; D008297:Male; D013274:Stomach Neoplasms / Q000276:immunology* / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D018664:Interleukin-12; D007371:Interferon-gamma