Successful therapeutic vaccination with integrase defective lentiviral vector expressing nononcogenic human papillomavirus E7 protein
Successful therapeutic vaccination with integrase defective lentiviral vector expressing nononcogenic human papillomavirus E7 protein
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DOI：
10.1002/ijc.27676
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发表时间：
2013-01-15
影响因子：
6.4
通讯作者：
Cara, Andrea
中科院分区：
文献类型：
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作者：
Grasso, Felicia;Negri, Donatella R. M.;Cara, Andrea
人乳头瘤病毒（HPV）高危基因型的持续感染是宫颈癌的原因，宫颈癌是世界范围内女性最常见的癌症之一，并且是与男性和女性的其他肛门生殖器和口咽癌相关的重要危险因素。在这里，我们设计了一种基于整合酶缺陷型慢病毒载体（IDLV）的治疗性疫苗，以递送突变的非致癌形式的HPV 16 E7蛋白，该蛋白被认为是HPV相关宫颈癌免疫治疗的肿瘤特异性抗原，与钙网蛋白（CRT）融合，钙网蛋白是一种能够增强主要组织相容性复合物I类抗原呈递的蛋白质（IDLV-CRT/E7）。IDLV-CRT/E7疫苗接种诱导了一个有效的和持久的E7特异性T细胞反应长达1年后，单次免疫。重要的是，用IDLV-CRT/E7单次免疫能够防止表达E7的TC-1肿瘤细胞的生长并根除小鼠中已建立的肿瘤。基于IDLV的疫苗在该临床前模型中诱导的强治疗效果表明，该策略可进一步开发为人类中安全且有吸引力的抗癌免疫疫苗。
Persistent infection with high risk genotypes of human papillomavirus (HPV) is the cause of cervical cancer, one of most common cancer among woman worldwide, and represents an important risk factor associated with other anogenital and oropharyngeal cancers in men and women. Here, we designed a therapeutic vaccine based on integrase defective lentiviral vector (IDLV) to deliver a mutated nononcogenic form of HPV16 E7 protein, considered as a tumor specific antigen for immunotherapy of HPV-associated cervical cancer, fused to calreticulin (CRT), a protein able to enhance major histocompatibility complex class I antigen presentation (IDLV-CRT/E7). Vaccination with IDLV-CRT/E7 induced a potent and persistent E7-specific T cell response up to 1 year after a single immunization. Importantly, a single immunization with IDLV-CRT/E7 was able to prevent growth of E7-expressing TC-1 tumor cells and to eradicate established tumors in mice. The strong therapeutic effect induced by the IDLV-based vaccine in this preclinical model suggests that this strategy may be further exploited as a safe and attractive anticancer immunotherapeutic vaccine in humans.