2005 Fiscal Year Final Research Report Summary
Application of dendritic cells and neutrophil-derived TRAIL to cancer cell therapy in children
| Project/Area Number |
16591039
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
MATSUZAKI Akinobu Kyushu University, Fuculty of Medicine, Professor, 医学部, 教授 (90238999)
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| Co-Investigator(Kenkyū-buntansha) |
SUMINOE Aiko Kyushu University, University Hospital, Research Associate, 大学病院, 助手 (80335968)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Childhood cancer / Dendritic cell / Immunotherapy / TRAIL / Neutrophil / Cell therapy |
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| Research Abstract |
1. Dendritic cell (DC) therapy in childhood cancer : Autologous DCs pulsed with tumor-specific peptides or tumor lysates were administered to patients with refractory/relapsed pediatric solid tumors. In one patient, the residual tumor disappeared following DC therapy and long-term remission was achieved. In other two patients, growth of the tumors was temporally suppressed for one or ten months. In these patients, an increase in number of CD8+HLA-DR+ lymphocytes and INF-γ+CD8+ lymphocytes were observed. DC-based immunotherapy may be feasible, well-tolerated and promising approach in the treatment of children with refractory malignant tumors.
2. Gene expression in DCs : In order to elucidate the functional characteristics of DCs, difference in gene expression was examined between adult peripheral blood (APB)- and umbilical cord blood (UCB)-derived DCs. The expression of calgranulin, which is speculated to be related to the establishment of immunotolernce, and cell cycle-related genes was significantly higher in UCB-DCs than APB-DCs, while the Th1-related cytokine genes were expressed much higher in APB-DCs. In addition, the expression of inflammatory cytokine genes increased depending on the DC maturation. The results may suggest functional difference in immune reactivity between UCB- and APB-DCs.
3. Anti-leukemic effect of neutrophil-derived TNF-related apoptosis-inducing ligand (TRAIL) : TRAIL was expressed in resting neutrophils at the mRNA and protein levels, and its expression was enhanced after stimulation with IFN-γ. Neutrophils expressed TRAIL on the cell surface and excrete it into the culture media. When Jurkat cells (leukemic cell line) were cultured with neutrophils in the presence of IFN-γ, the number of Jurkat cells undergoing apoptosis increased depending on the effector : target ratio. This cytotoxicity was suppressed partially by adding anti-TRAIL antibody to the media. The results suggest that neutrophils may exert their own antitumor effect by TRAIL.
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