Low-dose paclitaxel improves the therapeutic efficacy of recombinant adenovirus encoding CCL21 chemokine against murine cancer.
Low-dose paclitaxel improves the therapeutic efficacy of recombinant adenovirus encoding CCL21 chemokine against murine cancer.
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DOI：
10.1111/cas.12537
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发表时间：
2014-11
期刊：
影响因子：
5.7
通讯作者：
Wei YQ
中科院分区：
文献类型：
--
作者：
Chen P;Luo S;Wen YJ;Li YH;Li J;Wang YS;Du LC;Zhang P;Tang J;Yang DB;Hu HZ;Zhao X;Wei YQ
次级淋巴组织趋化因子（SLC/CCL 21）是CC趋化因子之一，通过在肿瘤部位共定位T细胞和树突状细胞而发挥有效的抗肿瘤免疫，并且目前针对人实体瘤进行测试。在这里，我们研究了重组腺病毒编码小鼠CCL 21（Ad-mCCL 21）与低剂量紫杉醇的组合是否会提高对小鼠癌症的治疗效果。携带B16-F10黑素瘤或4 T1乳腺癌的免疫活性小鼠用Ad-mCCL 21、紫杉醇或两种药物一起治疗。我们的研究结果表明，Ad-mCCL 21+低剂量紫杉醇与单独治疗相比更有效地减少肿瘤的生长，并显着延长荷瘤动物的生存时间。联合治疗的这些抗肿瘤作用与肿瘤部位的细胞因子网络改变、肿瘤细胞凋亡增强和肿瘤中新血管形成减少有关。重要的是，联合治疗引起了强烈的治疗性抗肿瘤免疫，这可以通过CD 4+或CD 8 + T淋巴细胞的耗竭而部分消除。总之，这些临床前评价可提供抗肿瘤免疫的联合策略，应考虑在临床试验中进行检测。
Secondary lymphoid tissue chemokine (SLC/CCL21), one of the CC chemokines, exerts potent antitumor immunity by co-localizing T cells and dendritic cells at the tumor site and is currently tested against human solid tumors. Here, we investigated whether the combination of recombinant adenovirus encoding murine CCL21 (Ad-mCCL21) with low-dose paclitaxel would improve therapeutic efficacy against murine cancer. Immunocompetent mice bearing B16-F10 melanoma or 4T1 breast carcinoma were treated with either Ad-mCCL21, paclitaxel, or both agents together. Our results showed that Ad-mCCL21 + low-dose paclitaxel more effectively reduced the growth of tumors as compared with either treatment alone and significantly prolonged survival time of the tumor-bearing animals. These antitumor effects of the combined therapy were linked to altered cytokine network at the tumor site, enhanced apoptosis of tumor cells, and decreased formation of new vessels in tumors. Importantly, the combined therapy elicited a strong therapeutic antitumor immunity, which could be partly abrogated by the depletion of CD4+ or CD8+ T lymphocytes. Collectively, these preclinical evaluations may provide a combined strategy for antitumor immunity and should be considered for testing in clinical trials.
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DOI：
10.1097/ppo.0b013e3181eb5066
发表时间：
2010-07
期刊：
Cancer journal (Sudbury, Mass.)
影响因子：
--
作者：
Emens LA
通讯作者：
Emens LA
影响因子：
5.2
作者：
Higashihara Y;Kato J;Nagahara A;Izumi K;Konishi M;Kodani T;Serizawa N;Osada T;Watanabe S
通讯作者：
Watanabe S
影响因子：
5.8
作者：
Chen, Gang;Emens, Leisha A.
通讯作者：
Emens, Leisha A.
影响因子：
4
作者：
Bodnar, Richard J.;Yates, Cecelia C.;Wells, Alan
通讯作者：
Wells, Alan
低剂量紫杉醇增强 GM-CSF 表面修饰的全肿瘤细胞疫苗对前列腺癌小鼠模型的抗肿瘤功效
影响因子：
5.8
作者：
He, Qiushan;Li, Jinlong;Gao, Jimin
通讯作者：
Gao, Jimin