Rastakhiz Saeedeh, Yazdani Mona, Shariat Sheida, Arab Atefeh, Momtazi-Borojeni Amir Abbas, Barati Nastaran, Mansourian Mercedeh, Amin Mohamdreza, Abbasi Azam, Saberi Zahra, Jalali Seyed Amir, Badiee Ali, Jaafari Mahmoud Reza
Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Science, Mashhad, Iran.
J Cell Biochem. 2019 Feb;120(2):1294-1303. doi: 10.1002/jcb.27090. Epub 2018 Oct 30.
The study was aimed at evaluating antitumor and immunomodulatory effects of liposomal vaccine composed of P5 human epidermal growth factor receptor 2 (HER2)/neu-derived peptide coupled to the surface of high-temperature nanoliposomes containing distearoylphosphocholine:distearoylphosphoglycerol:Chol:dioleoylphosphatidylethanolamine (DOPE) comprising monophosphoryl lipid A (MPL) adjuvant in HER2/neu overexpressing the breast cancer model. BALB/c mice bearing TUBO carcinoma were subcutaneously immunized with formulations containing 10 µg P5 peptide and 25 µg MPL three times with 2-week intervals. To determine immuno responses in immunized mice, the amount of released interferon-γ and IL-4 were measured by the enzyme-linked immunospot method and the flow cytometric analysis on the isolated splenocytes. The results demonstrated that tumor-bearing mice immunized with Lip/DOPE/MPL/P5 formulation had the most released interferon-γ and the highest cytotoxic T lymphocyte responses that led to the lowest tumor size and the longest survival time than those of other formulations. The results achieved by Lip/DOPE/MPL/P5 formulation could make it a suitable candidate to induce effective antigen-specific tumor immunity against breast cancer.
本研究旨在评估由P5人表皮生长因子受体2（HER2）/neu衍生肽偶联到含有二硬脂酰磷脂胆碱：二硬脂酰磷脂甘油：胆固醇：二油酰磷脂酰乙醇胺（DOPE）并包含单磷酰脂质A（MPL）佐剂的高温纳米脂质体表面组成的脂质体疫苗在HER2/neu过表达乳腺癌模型中的抗肿瘤和免疫调节作用。将携带TUBO癌的BALB/c小鼠皮下免疫含有10μg P5肽和25μg MPL的制剂，共三次，间隔2周。为了确定免疫小鼠中的免疫反应，通过酶联免疫斑点法和对分离的脾细胞进行流式细胞术分析来测量释放的干扰素-γ和IL-4的量。结果表明，与其他制剂相比，用Lip/DOPE/MPL/P5制剂免疫的荷瘤小鼠释放的干扰素-γ最多，细胞毒性T淋巴细胞反应最高，导致肿瘤尺寸最小，存活时间最长。Lip/DOPE/MPL/P5制剂取得的结果使其成为诱导针对乳腺癌的有效抗原特异性肿瘤免疫的合适候选物。
