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结直肠癌患者、非小细胞肺癌患者与健康供者来源的单核细胞衍生树突状细胞的比较。

Comparison of monocyte-derived dendritic cells from colorectal cancer patients, non-small-cell-lung-cancer patients and healthy donors.

机构信息

DanDrit Biotech A/S, Symbion Science Park, Copenhagen, Denmark.

出版信息

Vaccine. 2009 Dec 11;28(2):542-7. doi: 10.1016/j.vaccine.2009.09.129. Epub 2009 Nov 4.

Abstract

Dendritic cells (DCs) are bone marrow-derived professional antigen presenting cells. Due to their role as potent inducers of immune responses, these cells are widely used as adjuvant in experimental clinical settings for cancer immune therapy. We have developed a DC-based vaccine using autologous blood monocytes loaded with allogeneic tumor cell lysate rich in cancer/testis antigens. This vaccine has at present been tested for activity in three phase II clinical trials including two cohorts of patients with advanced colorectal cancer (CRC) and one cohort of patients with advanced non-small-cell-lung-cancer (NSCLC). In the present paper we retrospectively compare the maturation profile based on surface marker expression on DCs generated from the three patient cohorts and between cancer patient cohorts and a cohort of healthy donors. Vaccines were generated under cGMP conditions and phenotypic profiles of DC were analyzed by flow cytometry and the obtained data were used as a basis to set guideline values for our quality control of GMP produced DC vaccines. Each vaccine batch was analyzed for the expression of the surface maturation and differentiation molecules CD14, CD1a, CD83, CD86, MHC class II and CCR7, and the optimal expression pattern is considered as CD14(low), CD1a, CD83(high), CD86(high), MHC class II(high) and CCR7(high). In accordance with data from other studies including other types of cancer patients, especially breast cancer patients, we found that the maturation status of the DC batches depends on cancer type and correlates with clinical status of cancer patients included.

摘要

树突状细胞 (DCs) 是骨髓来源的专业抗原提呈细胞。由于其作为免疫反应有力诱导物的作用,这些细胞被广泛用作癌症免疫治疗的实验临床设置中的佐剂。我们使用负载有富含癌症/睾丸抗原的同种异体肿瘤细胞裂解物的自体血液单核细胞开发了一种基于 DC 的疫苗。目前,该疫苗已经在三项 II 期临床试验中进行了活性测试,包括两批晚期结直肠癌 (CRC) 患者和一批晚期非小细胞肺癌 (NSCLC) 患者。在本文中,我们回顾性地比较了来自三个患者队列的 DC 基于表面标志物表达的成熟谱,并比较了癌症患者队列和健康供者队列之间的成熟谱。疫苗是在 cGMP 条件下生成的,通过流式细胞术分析 DC 的表型谱,并将获得的数据用作我们 GMP 生产的 DC 疫苗质量控制的指南值的基础。对每批疫苗进行表面成熟和分化分子 CD14、CD1a、CD83、CD86、MHC 类 II 和 CCR7 的表达分析,最佳表达模式被认为是 CD14(low)、CD1a、CD83(high)、CD86(high)、MHC 类 II(high)和 CCR7(high)。与包括其他类型癌症患者在内的其他研究的数据一致,特别是乳腺癌患者,我们发现 DC 批次的成熟状态取决于癌症类型,并与纳入的癌症患者的临床状况相关。

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