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HSP70 对 HPV 相关肿瘤的修饰反应。

HSP70 modified response against HPV based tumor.

机构信息

Department of Virology, School of Medicine, Tarbiat Modares University, Tehran, Iran.

出版信息

Eur Rev Med Pharmacol Sci. 2013 Jan;17(2):228-34.

Abstract

BACKGROUND AND OBJECTIVES

DNA immunization is quite inventive vaccination strategies that engage the direct introduction of plasmid DNA encoding the desired antigen into the host. DNA vaccines expand strong protective responses against tumors. The desired target E7 oncogene products represent a target of choice for the therapeutic vaccination. The efficacy of vaccination is limited and it is often necessary to enhance the immune response by using adjuvant in order to achieve the desired responses. Numerous approaches have been applied to boost the effectiveness, such as the fusion or co-administration of cytokine and co-stimulatory molecules gene. Heat-shock protein 70 a family of chaperone proteins makes possible delivery of non-covalently bound peptide to MHC I molecules and influences peptide-specific CTL responses and cure treated individuals. HSP70 have been proposed as the affective adjuvant and expected to act as an appropriate substitute of both cytokine and co-stimulatory genes.

MATERIALS AND METHODS

In the current study, the impact of HSP70 co-delivery and HPV-E7 boosting on cellular immune responses and protection has been investigated by intramuscular injection of mixed DNA constructs.

RESULTS

Our results reveal that the target DNA vaccine can influence an E7-specific CTL response, which is imperative in the lysis of infected tumor cells, compared to negative control (p < 0.05). Additionally, treatment of tumor-bearing mice with pcDNA/E7 + HSP70 plasmid generates stronger immune responses and decreased significantly tumor sizes. Immunization with HSP-based vaccine with special target immunogene can induce potent and specific anti-tumor or anti-viral immune responses.

CONCLUSIONS

Co-administration of pcDNA/E7 + HSP70 plasmid was immunologically more effective than pcDNA/E7 alone. It was concluded that all the characteristics observed during our investigation demonstrate the potent adjuvant activities of HSP70 and could be an efficient approach to persuade dramatically E7-specific immune responses as future cervical cancer vaccine.

摘要

背景与目的

DNA 免疫是一种极具创意的疫苗接种策略,它通过直接将编码所需抗原的质粒 DNA 导入宿主来实现。DNA 疫苗可引发针对肿瘤的强烈保护反应。目的靶标 E7 癌基因产物是治疗性疫苗接种的首选靶标。疫苗接种的疗效有限,为了达到预期的效果,通常需要使用佐剂来增强免疫反应。为了提高疫苗的有效性,已经应用了许多方法,例如融合或共同给予细胞因子和共刺激分子基因。热休克蛋白 70(HSP70)家族是一组伴侣蛋白,它使非共价结合的肽递送到 MHC I 分子成为可能,并影响肽特异性 CTL 反应和治愈治疗个体。HSP70 已被提议作为有效的佐剂,有望替代细胞因子和共刺激基因。

材料与方法

在本研究中,通过肌肉内注射混合 DNA 构建体,研究了 HSP70 共递呈和 HPV-E7 增强对细胞免疫反应和保护的影响。

结果

我们的结果表明,与阴性对照相比(p < 0.05),靶 DNA 疫苗可以影响 E7 特异性 CTL 反应,这对裂解感染的肿瘤细胞至关重要。此外,用 pcDNA/E7 + HSP70 质粒治疗荷瘤小鼠会产生更强的免疫反应,并显著降低肿瘤大小。用具有特殊靶免疫基因的 HSP 为基础的疫苗进行免疫接种可以诱导有效的、特异性的抗肿瘤或抗病毒免疫反应。

结论

pcDNA/E7 + HSP70 质粒的共同给药比单独使用 pcDNA/E7 更具免疫效果。总之,我们研究过程中观察到的所有特征都表明 HSP70 具有强大的佐剂活性,并且可以作为一种有效的方法来促使 E7 特异性免疫反应显著增强,作为未来的宫颈癌疫苗。

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