Fluorinated Lipids Conjugated to Peptide Antigens do not Induce Immune Responses Against Cervical Cancer

W. M. Hussein, Saori Mukaida, Tzu-yu Liu, I. Toth, M. Skwarczynski
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引用次数: 2

Abstract

Background: Despite the high safety profile of peptide-based vaccines over conventional counterparts, the inability of small peptides to produce a strong immune response represents the main obstacle for the development of these types of vaccines. Introducing a self-adjuvanting moiety such as fluorinated lipids can overcome this problem. We have recently demonstrated that fluorinated lipids can induce humoral immune responses against associated peptide antigen; however, the ability of these amphiphilic lipids to elicit a desired cellular immune response to eradicate tumor cells has not been yet investigated. Methods: An in vivo assay was employed to evaluate the ability of fluorinated lipopeptides to eradicate tumor in mouse model. In this study, the double conjugation technique was used to synthesise fluorinated and non-fluorinated lipids conjugated to two cytotoxic T-lymphocyte (CTL) peptide epitopes derived from the E6 and E7 proteins of human papilloma virus (HPV). Results: Mice implanted with TC-1 tumor cells and immunised with fluorinated lipopeptides did not mount a strong cellular immune response, thus did not eradicate the tumors. In contrast, 60% of mice immunised with the non-fluorinated lipopeptide cleared the TC-1 tumor. Conclusion: This result indicated that fluorinated lipids lack of the ability to stimulate a strong cellular immunity despite their ability to elicit significant humoral immune responses.
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与肽抗原结合的氟化脂不会诱导对宫颈癌的免疫反应
背景:尽管基于肽的疫苗比传统疫苗具有更高的安全性,但小肽无法产生强烈的免疫反应是开发这类疫苗的主要障碍。引入自我调节的部分,如氟化脂类,可以克服这个问题。我们最近证明,氟化脂质可以诱导针对相关肽抗原的体液免疫反应;然而,这些两亲性脂质的能力,以引发所需的细胞免疫反应,以根除肿瘤细胞尚未研究。方法:采用体内实验方法评价氟化脂肽对小鼠肿瘤的根除作用。本研究采用双偶联技术合成了与人类乳头瘤病毒(HPV) E6和E7蛋白衍生的两个细胞毒性t淋巴细胞(CTL)肽表位偶联的氟化和非氟化脂质。结果:TC-1肿瘤细胞植入小鼠后,经氟化脂肽免疫后,未产生强烈的细胞免疫反应,因此未根除肿瘤。相比之下,60%用非氟化脂肽免疫的小鼠清除了TC-1肿瘤。结论:这一结果表明,氟化脂缺乏刺激细胞免疫的能力,尽管它们能够引起显著的体液免疫反应。
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