Establishment of tumor-specific dendritic cell vaccine pulsed by tumor-derived heat shock protein or cell fusion with tumor cells

肿瘤源性热休克蛋白或与肿瘤细胞融合的肿瘤特异性树突状细胞疫苗的建立

• 批准号: 11470247
• 负责人: TSUJITANI Shunichi
• 金额: $ 7.04万
• 依托单位: Tottori University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470247/
• 关键词: 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

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 … More 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

已有研究表明，DC与肿瘤细胞融合后可作为抗原提呈细胞（APC）发挥功能，并含有肿瘤特异性抗原。一些DC/Tumor融合细胞的临床试验表明，在晚期疾病患者中，肿瘤消退明显。在这项研究中，我们使用电融合技术产生融合细胞。在初步研究中，确定了最佳细胞数量（1.0 × 10^6个DC：1.0 × 10^6个肿瘤细胞/mL）和对齐电压（50 V，10秒）。采用ECM 2001电融合仪进行细胞融合，并通过荧光显微镜和流式细胞仪进行确认。DC与肿瘤细胞的融合率与细胞融合电压相关。而DC/肿瘤融合细胞的存活率随着电压的升高而降低。我们发现细胞融合的最佳电压为200 V，在此条件下融合率为6.12%，细胞存活率为68.33%。我们的数据并不上级于 ...更多信息 其他报道了DC和肿瘤细胞的电融合。DC/肿瘤融合细胞在肿瘤治疗中的实际应用需要进一步的研究。另一方面，RCAS 1是由针对人子宫腺癌细胞系SiSo产生的22-1-1抗体识别的肿瘤相关抗原。据报道，RCAS 1抑制受体表达细胞的生长，如多种人类癌细胞系、T、B和NK细胞，并诱导凋亡性细胞死亡。因此，RCAS 1的表达与食管鳞状细胞癌患者使用免疫组织化学方法结合抗RCAS 1抗体进行了检查。多因素分析显示RCAS 1表达是影响食管癌患者预后的独立因素之一。RCAS 1的表达与DC和肿瘤浸润淋巴细胞（TIL）的密度有关。肿瘤细胞对免疫细胞的反击机制有待阐明，以建立有效的DC治疗癌症。少

项目成果

Oka, Shinichi: "Correlation between the RCAS1 expression and the infiltrating immune cells in esophageal cancer"J Yonago Med Ass. 52. 52-63 (2001)

Oka, Shinichi：“食管癌中 RCAS1 表达与浸润性免疫细胞的相关性”J Yonago Med Ass。

岡 伸一: "食道癌におけるRCAS1発現の意義と腫瘍内浸潤リンパ球と樹状細胞に及ぼす影響の検討"米子医学雑誌. 52. 52-63 (2001)

Shinichi Oka：“食管癌中RCAS1表达的意义及其对瘤内浸润淋巴细胞和树突状细胞的影响”米子医学杂志52. 52-63 (2001)。