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Low-dose docetaxel enhances the anti-tumour efficacy of a human umbilical vein endothelial cell vaccine.
European Journal of Pharmaceutical Sciences ( IF 4.6 ) Pub Date : 2019-11-19 , DOI: 10.1016/j.ejps.2019.105163
Ling Zhou 1 , Meiyu Lu 1 , Weilan Zhong 1 , Junhou Yang 1 , Yancun Yin 2 , Minjing Li 2 , Defang Li 3 , Shumin Zhang 1 , Maolei Xu 1
Affiliation  

Our previous studies have indicated that human umbilical vein endothelial cell (HUVEC) vaccination appears to be a potentially promising anti-angiogenesis therapy, but the modest therapeutic anti-tumour efficiency limits its clinical use. This highlights the importance of identifying more potent therapeutic HUVEC vaccine strategies for clinical testing. In the present study, the immune-modulating doses of docetaxel (DOC) was combined with 1 × 106 viable HUVECs as a means to enhance the therapeutic anti-tumour efficiency of the HUVEC vaccine. Our results demonstrated that 5 mg/kg DOC administrated prior to HUVEC vaccine could most effectively assist HUVEC vaccine to display a remarkable suppression of tumour growth and metastasis as wells as a prolongation of survival time in a therapeutic procedure. CD31 immunohistochemical analysis of the excised tumours confirmed a significant reduction in vessel density after treatment with the HUVEC vaccine with 5 mg/kg DOC. Additionally, an increased HUVEC-specific antibody level, activated CTLs and an elevated IFN-γ level in cultured splenocytes were revealed after treatment with HUVEC vaccine with 5 mg/kg DOC. Finally, 5 mg/kg DOC coupled with the HUVEC vaccine led to induction of significant increases in CD8+T cells and decrease in Tregs in the tumour microenvironment. Taken together, all the results verified that 5 mg/kg DOC could assist HUVEC vaccine to elicit strong HUVEC specific humoral and cellular responses, which could facilitate the HUVEC vaccine-mediated inhibition of cancer growth and metastasis. These findings provide the immunological rationale for the combined use of immune-modulating doses of DOC and HUVEC vaccines in patients with cancer.

中文翻译:

小剂量多西紫杉醇可增强人脐静脉内皮细胞疫苗的抗肿瘤功效。

我们以前的研究表明,人脐静脉内皮细胞(HUVEC)疫苗似乎是潜在的有希望的抗血管生成疗法,但适度的治疗性抗肿瘤功效限制了其临床应用。这突出了确定用于临床测试的更有效的HUVEC治疗性疫苗策略的重要性。在本研究中,将多西他赛(DOC)的免疫调节剂量与1×106种可行的HUVEC结合使用,以增强HUVEC疫苗的治疗性抗肿瘤功效。我们的结果表明,在HUVEC疫苗之前施用5 mg / kg DOC可以最有效地帮助HUVEC疫苗在治疗过程中显着抑制肿瘤生长和转移以及延长生存时间。切除的肿瘤的CD31免疫组织化学分析证实,用HUVEC疫苗和5 mg / kg DOC治疗后,血管密度显着降低。另外,在用5mg / kg DOC的HUVEC疫苗处理后,在培养的脾细胞中显示出HUVEC特异性抗体水平升高,活化的CTL和IFN-γ水平升高。最终,5 mg / kg DOC加上HUVEC疫苗导致在肿瘤微环境中诱导CD8 + T细胞显着增加和Treg降低。两者合计,所有结果证明5 mg / kg DOC可以帮助HUVEC疫苗引起强烈的HUVEC特异性体液和细胞反应,从而可以促进HUVEC疫苗介导的癌症生长和转移抑制。
更新日期:2019-11-19
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