缺失型重组人乳头瘤病毒16型E7蛋白的临床前免疫原性和抗肿瘤疗效

Pre-clinical immunogenicity and anti-tumour efficacy of a deleted recombinant human papillomavirus type 16 E7 protein.

作者信息

Hallez Sophie, Brulet Jean-Marc, Vandooren Caroline, Maudoux Frédéric, Thomas Séverine, Heinderickx Michel, Bollen Alex, Wattiez Ruddy, Jacquet Alain

机构信息

Chimie Biologique, Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, 6041 Gosselies, Belgium.

出版信息

Anticancer Res. 2004 Jul-Aug;24(4):2265-75.

PMID:15330171

Abstract

BACKGROUND

Current vaccination strategies against Human papillomavirus (HPV)-induced ano-genital cancers mostly target E7 from HPV16. However, the oncogenic nature of E7 raises potential human safety issues. Although the modifications abrogating the E7 transforming potential have been well characterized, their effect on E7 immunogenicity has been poorly studied. In this study, we evaluated the vaccine potential of an HPV16 E7 protein deleted from the entire pRb-binding motif.

MATERIALS AND METHODS

Purified recombinant deleted (E7delta21-26) and wild-type (His6-E7 and E7WT) E7 proteins were studied in pre-clinical mice models.

RESULTS

In C57BL/6 mice, E7delta21-26 formulated with the Quil A adjuvant generated systemic E7-specific cytotoxic T-cell and antibody responses similar to those induced following His6-E7/Quil A and E7WT/Quil A vaccinations. E7delta21-26/Quil A injections efficiently protected animals from challenge with the HPV16-expressing tumours, C3 and TC-1. Moreover, therapeutic vaccination with adjuvant-modified E7 suppressed or significantly decreased C3 tumour outgrowth.

CONCLUSION

E7delta21-26 could represent a safe and efficient vaccine candidate against E7-containing tumour cells.

摘要

背景

目前针对人乳头瘤病毒（HPV）引起的肛门生殖器癌的疫苗接种策略主要针对HPV16的E7蛋白。然而，E7的致癌特性引发了潜在的人类安全问题。尽管消除E7转化潜能的修饰已得到充分表征，但它们对E7免疫原性的影响研究较少。在本研究中，我们评估了缺失整个pRb结合基序的HPV16 E7蛋白的疫苗潜力。

材料与方法

在临床前小鼠模型中研究纯化的重组缺失型（E7delta21 - 26）和野生型（His6 - E7和E7WT）E7蛋白。

结果

在C57BL/6小鼠中，用Quil A佐剂配制的E7delta21 - 26产生的全身性E7特异性细胞毒性T细胞和抗体反应与His6 - E7/Quil A和E7WT/Quil A疫苗接种后诱导的反应相似。E7delta21 - 26/Quil A注射有效地保护动物免受表达HPV16的肿瘤C3和TC - 1的攻击。此外，用佐剂修饰的E7进行治疗性疫苗接种可抑制或显著减少C3肿瘤的生长。