Phase I clinical trial of autologous ascites-derived exosomes combined with GM-CSF for colorectal cancer.
Phase I clinical trial of autologous ascites-derived exosomes combined with GM-CSF for colorectal cancer.
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DOI：
10.1038/mt.2008.1
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发表时间：
2008-04
期刊：
影响因子：
--
通讯作者：
Li G
中科院分区：
文献类型：
--
作者：
Dai S;Wei D;Wu Z;Zhou X;Wei X;Huang H;Li G
外来体是由多种细胞类型分泌的小膜囊泡。来源于树突状细胞（Dex）、肿瘤细胞（Tex）和恶性积液的外泌体显示出免疫调节功能，并且甚至处于癌症治疗的临床试验中。在这项研究中，我们报告了腹水来源的外泌体（Aex）与粒细胞-巨噬细胞集落刺激因子（GM-CSF）联合免疫治疗结直肠癌（CRC）的I期临床试验。通过蔗糖/D2 O密度梯度超离心分离的Aex是60-90-nm的囊泡，其含有外泌体和肿瘤相关癌胚抗原（CEA）的多种免疫调节标记物。入选40例HLA-A0201+CEA+的晚期结直肠癌患者，随机分为Aex单药治疗组和Aex + GM-CSF治疗组。两组患者均接受了每周一次的共四次皮下免疫接种。我们发现这两种疗法都是安全和耐受性良好的，Aex联合GM-CSF而不是Aex单独可以诱导有益的肿瘤特异性抗肿瘤细胞毒性T淋巴细胞（CTL）应答。因此，本研究提示Aex联合GM-CSF免疫治疗结直肠癌是安全可行的，可作为晚期结直肠癌免疫治疗的一种选择。
Exosomes are small membrane vesicles that are secreted by a multitude of cell types. The exosomes derived from dendritic cells (Dex), tumor cells (Tex), and malignant effusions demonstrate immunomodulatory functions, and are even under clinical trial for cancer treatments. In this study we report the phase I clinical trial of the ascites-derived exosomes (Aex) in combination with the granulocyte–macrophage colony-stimulating factor (GM-CSF) in the immunotherapy of colorectal cancer (CRC). The Aex isolated by sucrose/D2O density gradient ultracentrifugation are 60–90-nm vesicles that contain the diverse immunomodulatory markers of exosomes and tumor-associated carcinoembryonic antigen (CEA). Totally 40 patients (HLA-A0201+CEA+) with advanced CRC were enrolled in the study, and randomly assigned to treatments with Aex alone or Aex plus GM-CSF. Patients in both groups received a total of four subcutaneous immunizations at weekly intervals. We found that both therapies were safe and well tolerated, and that Aex plus GM-CSF but not Aex alone can induce beneficial tumor-specific antitumor cytotoxic T lymphocyte (CTL) response. Therefore, our study suggests that the immunotherapy of CRC with Aex in combination with GM-CSF is feasible and safe, and thus can serve as an alternative choice in the immunotherapy of advanced CRC.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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DOI：
10.1007/s00109-006-0102-0
发表时间：
2006-12
期刊：
Journal of molecular medicine (Berlin, Germany)
影响因子：
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作者：
Dai S;Zhou X;Wang B;Wang Q;Fu Y;Chen T;Wan T;Yu Y;Cao X
通讯作者：
Cao X
DOI：
10.1073/pnas.0603466103
发表时间：
2006-08-01
影响因子：
11.1
作者：
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通讯作者：
Sprent, Jonathan