Establishment of tumor-specific dendritic cell vaccine pulsed by tumor-derived heat shock protein or cell fusion with tumor cells
| Project/Area Number |
11470247
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Tottori University |
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Principal Investigator |
TSUJITANI Shunichi Tottori University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (30188544)
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| Co-Investigator(Kenkyū-buntansha) |
KONDO Akira Tottori University Hospital, Assistant Professor, 医学部・附属病院, 助手 (90304211)
GOMYO Yoshihito Tottori University, Faculty of Medicine, Assistant Professor, 医学部, 助手 (20314578)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥11,000,000 (Direct Cost: ¥11,000,000)
Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1999: ¥7,600,000 (Direct Cost: ¥7,600,000)
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| Keywords | Cancer / Dendritic cell / Electrofusion / RCAS1 / Immune evasion / 細胞融合 / 腫瘍特異的免疫 / 腫瘍 / 熱ショック蛋白 / 癌ワクチン |
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| Research Abstract |
Some previous reports indicated that fusion cells of DCs and tumor cells could function as antigen-presenting cells (APCs) containing tumor specific antigens. Several clinical trials with DC/Tumor fusion cells demonstrated an obvious tumor regression in patients with advanced stage of disease. In this study, we used electrofusion techniques for producing the fusion cells. In a preliminary study, the optimal cell numbers (1.0x10^6 of DCs : 1.0x10^6 of tumor cells/mL) and alignment voltage (50 V for 10 sec) were determined. Cell fusion was performed using ECM2001 electrofusion apparatus and confirmed by fluorescent microscopy and flow cytometry. The fusion ratio of DCs and tumor cells correlated with the voltage for cell fusion. However, the viability of DC/tumor fusion cells had decreased as the elevation of the voltage. We found that the optimal voltage for cell fusion was 200 V. This condition achieved 6.12 % of fusion ratio and 68.33 % of cell viability. Our data are not superior to
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the other reports for electrofusion of DCs and tumor cells. Further studies are requested for practical use of DC/tumor fusion cells in cancer therapy. On the other hand, RCAS1 is a tumor-associated antigen recognized by 22-1-1 antibody raised against a human uterine adenocarcinoma cell line, SiSo. It has been reported that RCAS1 inhibited the growth of receptor-expressing cells, such as a variety of human cancer cell lines, T, B and NK cells and induced apoptotic cell death. Thus, RCAS1 expression was examined in patients with esophageal squamous cell carcinomas using an immunohistochemical method in conjunction with anti-RCAS1 antibody. Multivariate analyses showed that RCAS1 expression was one of the independent prognostic factors in patients with esophageal cancer. RCAS1 expression was related with the population density of DC and tumor-infiltrating lymphocytes (TIL). The mechanisms of counterattack by tumor cells against immune cells should be clarified to establish an effective DC treatment for cancer. Less
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Report
(4 results)
Research Products
(2 results)
