经卡介苗活化的树突状细胞疫苗治疗胰腺癌的基础及临床运用展望——暨向2011年诺贝尔医学奖得主Ralph Steinman教授致敬

目的探讨经卡介苗(BCG)活化的树突状细胞(DC)疫苗体外直接抗胰腺癌细胞Panc02的机制,以及观察经不同部位注射DC疫苗抗小鼠胰腺癌移植瘤的效应。方法从C57BL/6小鼠骨髓中诱导培养DC,并予以BCG促成熟,用流式细胞技术检测DC成熟度,CCK-8细胞计数检测DC直接抑制Panc02增殖情况,流式细胞仪检测BCG促成熟DC表面凋亡诱导配体(TRAIL)的表达量。C57BL/6小鼠皮下接种Panc02胰腺癌细胞制成荷瘤小鼠,第7 d予以DC疫苗注射免疫治疗(DC疫苗为经Panc02细胞冻融抗原致敏后BCG促成熟的DC),分为3组:瘤内注射生理盐水组、皮下注射DC疫苗组和瘤内注射DC疫苗组,...

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Published in临床肝胆病杂志 Vol. 28; no. 8; pp. 592 - 597
Main Author 刘文佳 朱浩 吕瑛 李振磊 张松 裴庆山 邹晓平
Format Journal Article
LanguageChinese
Published 南京大学医学院附属鼓楼医院消化科,南京,210008 2012
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Summary:目的探讨经卡介苗(BCG)活化的树突状细胞(DC)疫苗体外直接抗胰腺癌细胞Panc02的机制,以及观察经不同部位注射DC疫苗抗小鼠胰腺癌移植瘤的效应。方法从C57BL/6小鼠骨髓中诱导培养DC,并予以BCG促成熟,用流式细胞技术检测DC成熟度,CCK-8细胞计数检测DC直接抑制Panc02增殖情况,流式细胞仪检测BCG促成熟DC表面凋亡诱导配体(TRAIL)的表达量。C57BL/6小鼠皮下接种Panc02胰腺癌细胞制成荷瘤小鼠,第7 d予以DC疫苗注射免疫治疗(DC疫苗为经Panc02细胞冻融抗原致敏后BCG促成熟的DC),分为3组:瘤内注射生理盐水组、皮下注射DC疫苗组和瘤内注射DC疫苗组,1周后再治疗1次,第2次治疗后15 d处死小鼠,观察不同治疗抗肿瘤的效果。结果 BCG活化后DC疫苗成熟度明显增加,其表型CD86表达增加;经BCG活化成熟的DC能直接抑制Panc02细胞生长,这一作用可被TRAIL抗体部分抑制,且流式细胞术检测发现成熟DC表面分子TRAIL明显高于未经BCG促成熟组未成熟DC。肿瘤体重:瘤内注射DC疫苗组〈皮下注射DC疫苗组〈瘤内注射生理盐水组(P〈0.01)。结论 BCG活化的胰腺癌DC疫苗的生物活性明显增加,并可通过TRAIL这一途径直接杀伤肿瘤细胞;且经BCG活化的DC疫苗瘤内注射免疫治疗抗肿瘤作用更强。
Bibliography:LIU Wen -fia, ZHU Hao, LYU Ying, et al. ( Department of Gastroenterology, the Affiliated Drum Tower Hospital of Nanjing University Medi- cal School, Nanjing 210008, China)
Objective To study the direct anti - tumor effects of the Mycobacterium boris bacillus Calmette - Guerin (BCG) - activated dendritic cell (DC) vaccine in vitro and in vivo. Methods DCs were harvested from bone marrow of C57BL/6 mice and cultured with BCG to stimulate maturation. Activated DCs were evaluated by flow cytometry (FCM). Activated DCs were co - cultured with the pancreatic tumor cell line, Pane02, and cytotoxic response was measured by the CCK - 8 kit. The frequency of activated DCs expressing tumor necrosis factor - related apoptosis - inducing ligand (TRAIL) was measured by FCM, and TRAIL mRNA levels were detected by real - time PCR. C57BL/6 mice were implanted with Pane02 tumor cells by subcutaneous inoculation, and on the seventh day were randomly divided into three groups: untreated control, injected with saline; DC vaccine -
ISSN:1001-5256