Department of Medical Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
Immunogenetic and Cell Culture Department, Immunology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
J Control Release. 2019 Jun 10;303:223-236. doi: 10.1016/j.jconrel.2019.04.019. Epub 2019 Apr 15.
Liposomal peptide-based vaccines can potentially suppress cancer cells proliferation in the host. To enhance the effectiveness of vaccination against cancer, additional strategies should also be employed. One strategy to promote peptide-based vaccine efficacy and induce powerful immune responses, is simultaneous activation of CD4 and CD8 T cells. To address this problem, we tested the efficacy of a nano-liposomal vaccine containing P5 peptide, a cytotoxic T lymphocytes (CTL) specific peptide derivative of rat HER2/neu protein, Pan HLA-DR (PADRE) peptide, a universal CD4 T helper cell epitope and monophosphoryl lipid A (MPL) a toll-like receptor 4 ligand. We observed potent CD8 T cell immune responses in TUBO mice vaccinated with liposomal P5 peptide in combination with PADRE and MPL. Also, this formulation remarkably improved anti-tumor effects against cells overexpressing HER2 in BALB/c mice compared to liposomal vaccine containing P5 only. Furthermore, we found that vaccination with Lip-P5- Integrated PADRE-MPL formulation significantly induced IFN-γ production, increased CD8 T cells numbers and enhanced survival compared to other groups of treated mice. In conclusion, our study indicated that Lip-P5-Integrated PADRE-MPL, after further confirmatory investigations, could be employed as a promising vaccine to generate potent CTL anti-tumor immune responses that could be beneficial to treatment of HER2 breast cancer.
基于脂质体的肽疫苗可以潜在地抑制宿主中癌细胞的增殖。为了提高癌症疫苗的有效性，还应采用其他策略。一种增强基于肽的疫苗效力并诱导强大免疫应答的策略是同时激活 CD4 和 CD8 T 细胞。为了解决这个问题，我们测试了含有 P5 肽的纳米脂质体疫苗的功效，P5 肽是大鼠 HER2/neu 蛋白的细胞毒性 T 淋巴细胞（CTL）特异性肽衍生物，Pan HLA-DR（PADRE）肽是一种通用的 CD4 T 辅助细胞表位，单磷酰脂质 A（MPL）是 Toll 样受体 4 配体。我们观察到 TUBO 小鼠用脂质体 P5 肽与 PADRE 和 MPL 联合接种后产生了强烈的 CD8 T 细胞免疫应答。此外，与仅含有 P5 的脂质体疫苗相比，该制剂显著提高了 BALB/c 小鼠中过表达 HER2 的细胞的抗肿瘤效果。此外，我们发现与其他治疗组相比，用 Lip-P5- 整合 PADRE-MPL 制剂接种可显著诱导 IFN-γ 的产生，增加 CD8 T 细胞数量并提高存活率。总之，我们的研究表明，Lip-P5- 整合 PADRE-MPL 在进一步的确认性研究后，可作为一种有前途的疫苗，以产生有效的 CTL 抗肿瘤免疫应答，这可能对治疗 HER2 乳腺癌有益。
