Tumor specific immunotherapy using dendritic cells generated from allogeneic peripheral stem cell.

使用同种异体外周干细胞产生的树突状细胞进行肿瘤特异性免疫治疗。

基本信息

批准号：
14370520
负责人：
TACHIBANA Masaaki
金额：
$ 9.22万
依托单位：
Tokyo Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

In order to develop a less invasive treatment strategy for advanced urological cancer, we. examined the potential of cell-immunotherapy using dendritic cells (DCs) generated from peripheral blood mono nuclear cells of kinsman. 2002 as a, we synthesized HLA-A2 and -A24 restricted epitope peptides prostate specific membrane antigen epitope peptide for prostate cancer and melanoma antigen-3 epitope peptide for bladder cancer. DCs loaded with each major histocompatibility antigen class 1 restricted epitope peptide were able to induce corresponding antigen- specific cytotoxic T-lymphocytes capable to lyse the target cancer cells in vitro. The immunotherapy using autologous monocyte-derived DCs loaded with these epitope peptides, which was introduced to at least either HLA-A2 or -A24 positive patients with bladder cancer and prostate cancer in preceding year, was carried out through second fiscal year 2003. There were patients showed a >50% reduction in the size of metastatic tumor or in ser … More ological tumor marker. No severe adverse effect was observed in all patients treated with this therapy. These results suggested that the DC based immunotherapy was safe and, effective for patients with cancer resistant to conventional treatment. We also identified novel cancer specific antigens of bladder cancer by using serologic identification of recombinant cDNA expression cloning method, and synthesized the HLA -A24 restricted epitope peptides of these antigens. It was possible to elicit HLA-A24 positive bladder cancer cell lysis by DCs loaded with these epitope peptides in vitro. As for the main purpose of this study, the induction of DCs from allogeneic peripheral stem cells, we demonstrated that CD34 positive progenitor cells were separated from peripheral blood with the purity of 85.3% by using magnetic cell selection system. This made it appear that the application of this system enables to make cell conditioning more efficient. Furthermore, to examine the effect of DCs generated from allogeneic CD34 progenitor cells to the donor lymphocytes, we carried out mixed culture experiment using DCs from one of twin, lymphocytes from the other of twin, parents and non-kinsman in the same way of mixed lymphocyte culture. The rejection test of DCs by the lymphocytes of non-kinsman showed that the stimulation index was 3.6 comparable to the results in kin group. This result suggested that it might not be necessary to limit the source of DCs to CD34 progenitor cells from kinsman. Less

为了开发一种针对晚期泌尿系癌症的侵入性较小的治疗策略，我们研究了使用 kinsman 2002 的外周血单核细胞产生的树突状细胞 (DC) 的潜力，我们合成了 HLA-A2 和 -。用于前列腺癌的 A24 限制性表位肽前列腺特异性膜抗原表位肽和用于膀胱癌的黑色素瘤抗原 3 表位肽负载有每种主要组织相容性抗原类别的 DC。 1个表位肽被限制诱导相应的抗原特异性细胞毒性T淋巴细胞，能够在体外裂解靶癌细胞，使用负载这些表位肽的自体单核细胞衍生的DC，将其至少引入HLA-A2或HLA-A2。 -截至2003年第二财年，对前一年患有膀胱癌和前列腺癌的A24阳性患者进行了研究。这些患者的转移性肿瘤大小减少了>50%或在血清学肿瘤标志物中，在接受该疗法治疗的所有患者中均未观察到严重的副作用。这些结果表明，基于 DC 的免疫疗法对于对常规治疗有抵抗力的癌症患者是安全且有效的。采用血清学鉴定重组cDNA表达克隆方法对膀胱癌特异性抗原进行鉴定，并合成这些抗原的HLA-A24限制性表位肽，可以诱导HLA-A24阳性膀胱癌细胞裂解。体外负载这些表位肽的DCs 对于本研究的主要目的，从同种异体外周干细胞诱导DCs，我们证明使用磁性细胞从外周血中分离出纯度为85.3%的CD34阳性祖细胞。这表明该系统的应用可以使细胞调理更加有效。此外，为了检查同种异体 CD34 祖细胞产生的 DC 对供体淋巴细胞的影响。以双胞胎之一的DC、双胞胎、父母和非亲属的淋巴细胞进行混合培养实验，非亲属的淋巴细胞对DC的排斥反应结果为： 3.6 与 kin 组的结果相当该结果表明可能没有必要将 DC 来源限制为来自 kinsman 的 CD34 祖细胞。

项目成果

期刊论文数量（44）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

橘政昭: "癌免疫細胞治療の現況と将来展望(造血幹細胞の癌免疫治療への応用)"再生医療(日本再生医療学会雑誌). 3巻増刊. 182 (2004)

橘正明：“癌症免疫细胞治疗的现状和未来展望（造血干细胞在癌症免疫治疗中的应用）”再生医学（日本再生医学会杂志）第3卷特刊（2004年）。

DOI：
发表时间：
期刊：
影响因子：
0
作者：
通讯作者：

Screening of HLA-A24-restricted epitope peptides from prostate-specific membrane antigen that induce specific antitumor cytotoxic T lymphocytes.

从诱导特异性抗肿瘤细胞毒性 T 淋巴细胞的前列腺特异性膜抗原中筛选 HLA-A24 限制性表位肽。

DOI：
发表时间：
2002
期刊：
Clin Cancer Res 8
影响因子：
0
作者：
Takahashi K;Horiguchi Y
通讯作者：
Horiguchi Y

橘政昭: "泌尿器科癌に対する樹状細胞(dendritic cells ; DC)治療の現状と将来展望"腎臓. 187-196 (2003)

Masaaki Tachibana：“泌尿系统癌症的树突状细胞 (DC) 治疗的现状和未来前景”Kidney 187-196 (2003)。

DOI：
发表时间：
期刊：
影响因子：
0
作者：
通讯作者：

Adenovirus- mediated gene transduction of truncated IkappaBalpha enhances radiosensitivity in human colon cancer cells.

腺病毒介导的截短 IkappaBalpha 基因转导增强了人类结肠癌细胞的放射敏感性。

DOI：
发表时间：
2003
期刊：
Cancer Sci. 94
影响因子：
0
作者：
Mukogawa T;Koyama F;Tachibana M;Takayanagi A;Shimizu N;Fujii H;Ueno M;Matsumoto H;Takeuchi T;Nakajima Y.
通讯作者：
Nakajima Y.

Increased number of cyclin D 1 gene copies detected by fluorescence in situ hybridization in initially organ-confined renal cell carcinomas with subsequent distant metastasis.

通过荧光原位杂交检测到最初局限于器官的肾细胞癌随后出现远处转移，细胞周期蛋白 D 1 基因拷贝数增加。