Mahmoodi Shirin, Nezafat Navid, Barzegar Abolfazl, Negahdaripour Manica, Nikanfar Ali R, Zarghami Nosratollah, Ghasemi Younes
Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, P.O. Box 5144853431, Tabriz, Iran.
Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Shiraz University of Medical Sciences, P.O. Box 71345-1583, Shiraz, Iran.
Curr Pharm Biotechnol. 2016;17(12):1100-1114. doi: 10.2174/1389201017666160914191106.
Breast cancer (BC) remains as one of the important causes of cancer deaths among women globally. Therefore, finding an effective treatment for BC is really needed. Cancer immunotherapy, as an emerging field, has a notable role in BC therapy. Peptide vaccines possess an outstanding role among different strategies in cancer immunotherapy. In vaccine design for cancer, induction of cellular and humoral immune responses should be considered. In the current study, cytolytic T lymphocytes (CTL) epitopes were evoked from human epidermal growth factor receptor (HER2), mucin 1 protein (MUC1), and heparanase antigenic proteins; and helper T lymphocytes (HTL) epitopes were determined from survivin protein by various immunoinformatics servers. Furthermore, our vaccine peptide contains several linear and conformational B cell epitopes that can induce humoral immunity. In order to elicit broad cellular and humoral immune responses, Por B protein from Neisseria meningitides, which is one of the toll like receptor 2 (TLR2) agonists, was utilized as an adjuvant in the vaccine construct. The designed peptide vaccine contains the extracellular domain of murine ULBP-like transcript 1 (MULT1), which binds to a natural killer group 2 member D (NKG2D) receptor with a high affinity and has a key role in triggering the innate immune response. All the mentioned segments were fused together by functional and structural amino acid linkers. Taken together, we project that our vaccine construct can potentially induce cellular, humoral, and innate immune responses in BC patients.
乳腺癌(BC)仍是全球女性癌症死亡的重要原因之一。因此,确实需要找到一种有效的乳腺癌治疗方法。癌症免疫疗法作为一个新兴领域,在乳腺癌治疗中具有显著作用。肽疫苗在癌症免疫疗法的不同策略中发挥着突出作用。在癌症疫苗设计中,应考虑诱导细胞免疫和体液免疫反应。在本研究中,通过各种免疫信息学服务器从人表皮生长因子受体(HER2)、粘蛋白1蛋白(MUC1)和乙酰肝素酶抗原蛋白中诱发细胞毒性T淋巴细胞(CTL)表位;并从生存素蛋白中确定辅助性T淋巴细胞(HTL)表位。此外,我们的疫苗肽包含几个可诱导体液免疫的线性和构象性B细胞表位。为了引发广泛的细胞免疫和体液免疫反应,将来自脑膜炎奈瑟菌的Por B蛋白(其是Toll样受体2(TLR2)激动剂之一)用作疫苗构建体中的佐剂。设计的肽疫苗包含小鼠ULBP样转录本1(MULT1)的细胞外结构域,其与自然杀伤细胞组2成员D(NKG2D)受体具有高亲和力结合,并在触发先天免疫反应中起关键作用。所有上述片段通过功能性和结构性氨基酸接头融合在一起。综上所述,我们推测我们的疫苗构建体可能在乳腺癌患者中诱导细胞免疫、体液免疫和先天免疫反应。