The Key Laboratory of Traditional Chinese Medicine Prescription Effect and Clinical Evaluation of State Administration of Traditional Chinese Medicine, School of Pharmacy, Binzhou Medical University, Yantai 264003, China.
Medicine and Pharmacy Research Center, Binzhou Medical University, Yantai 264003, China.
Eur J Pharm Sci. 2020 Jan 15;142:105163. doi: 10.1016/j.ejps.2019.105163. Epub 2019 Nov 19.
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 × 10 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 CD8T 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.
我们之前的研究表明，人脐静脉内皮细胞（HUVEC）疫苗接种似乎是一种有潜力的抗血管生成治疗方法，但适度的治疗抗肿瘤效率限制了其临床应用。这凸显了确定更有效的治疗性 HUVEC 疫苗策略用于临床测试的重要性。在本研究中，我们将免疫调节剂量的多西他赛（DOC）与 1×10 个活的 HUVEC 联合使用，以增强 HUVEC 疫苗的治疗抗肿瘤效率。我们的结果表明，在 HUVEC 疫苗接种前给予 5mg/kg 的 DOC 可以最有效地帮助 HUVEC 疫苗显著抑制肿瘤生长和转移，并延长治疗过程中的生存时间。对切除肿瘤的 CD31 免疫组化分析证实，用 5mg/kg DOC 处理后，血管密度显著降低。此外，在用 5mg/kg DOC 处理 HUVEC 疫苗后，培养的脾细胞中 HUVEC 特异性抗体水平升高、激活的 CTL 和 IFN-γ 水平升高。最后，5mg/kg DOC 与 HUVEC 疫苗联合使用导致肿瘤微环境中 CD8T 细胞显著增加，Tregs 减少。综上所述，所有结果均证实 5mg/kg DOC 可辅助 HUVEC 疫苗引发强烈的 HUVEC 特异性体液和细胞反应，从而促进 HUVEC 疫苗介导的肿瘤生长和转移抑制。这些发现为癌症患者联合使用免疫调节剂量的 DOC 和 HUVEC 疫苗提供了免疫学依据。
