Department of Human Science and Promotion of the Quality of Life, San Raffaele University Rome, Via di Val Cannuta 247, 00166 Rome, Italy.
Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy.
Nutrients. 2020 May 14;12(5):1417. doi: 10.3390/nu12051417.
The survival rate for head and neck cancer patients has not substantially changed in the last two decades. We previously showed that two rV-T intratumoral injections induced an efficient antitumor response and rejection of transplanted Neu (rat oncogene-encoded protein)-overexpressing salivary gland tumor cells in BALB-T mice (BALB/c mice transgenic for the rat oncogene). However, reiterated poxviral vaccinations increase neutralizing antibodies to viral proteins in humans that prevent immune response against the recombinant antigen expressed by the virus. Curcumin (CUR) is a polyphenol with antineoplastic and immunomodulatory properties. The aim of this study was to employ CUR administration to boost the anti-Neu immune response and anticancer activity induced by one rV-T intratumoral vaccination in BALB-T mice. Here, we demonstrated that the combined rV-nT+CUR treatment was more effective at reducing tumor growth and increasing mouse survival, anti-Neu humoral response, and IFN-γ/IL-2 T-cell release in vitro than the individual treatment. rV-T+CUR-treated mice showed an increased infiltration of CD4/CD8 T lymphocytes within the tumor as compared to those that received the individual treatment. Overall, CUR enhanced the antitumoral effect and immune response to Neu induced by the rV-T vaccine in mice. Thus, the combined treatment might represent a successful strategy to target ErbB2/Neu-overexpressing tumors.
在过去的二十年中,头颈部癌症患者的存活率并没有显著提高。我们之前的研究表明,两次 rV-T 瘤内注射可诱导有效的抗肿瘤反应,并排斥 BALB-T 小鼠(携带大鼠癌基因的 BALB/c 小鼠)中移植的 Neu(大鼠癌基因编码蛋白)过表达涎腺肿瘤细胞。然而,反复痘病毒疫苗接种会增加人体对病毒蛋白的中和抗体,从而阻止针对病毒表达的重组抗原的免疫反应。姜黄素(CUR)是一种具有抗肿瘤和免疫调节特性的多酚。本研究旨在通过 CUR 给药来增强由单次 rV-T 瘤内接种诱导的抗 Neu 免疫反应和抗癌活性在 BALB-T 小鼠中。在这里,我们证明了 rV-nT+CUR 联合治疗在减少肿瘤生长和提高小鼠存活率、抗 Neu 体液反应以及体外 IFN-γ/IL-2 T 细胞释放方面比单独治疗更有效。与接受单独治疗的小鼠相比,rV-T+CUR 治疗的小鼠肿瘤内 CD4/CD8 T 淋巴细胞浸润增加。总的来说,CUR 增强了 rV-T 疫苗诱导的针对 Neu 的抗肿瘤作用和免疫反应。因此,联合治疗可能是针对 ErbB2/Neu 过表达肿瘤的一种成功策略。