Kadish Anna S, Einstein Mark H
Departments of Pathology, Obstetrics and Gynecology & Women's Health, Albert Einstein College of Medicine, 1695 Eastchester Road, Suite 601, Bronx, NY 10461, USA.
Curr Opin Oncol. 2005 Sep;17(5):456-61. doi: 10.1097/01.cco.0000174038.92526.29.
To review novel immunologic strategies for the prevention and treatment of human papillomavirus infection and associated diseases. Both animal model systems and human protocols are discussed.
Many vaccine platforms for both prevention of human papillomavirus infection and treatment of associated disease have been developed. Virus-like particle constructs containing human papillomavirus capsid proteins have been shown to protect against human papillomavirus infection. Novel peptide or protein constructs containing modified E6 or E7 proteins, novel adjuvants, fusion proteins such as immunoglobulin-G-heavy chain E7, or heat shock proteins have been made as therapeutic modalities. In addition, many new recombinant vaccine vectors such as vaccinia, Listeria species, adenovirus, Semliki Forest vectors, and others have been developed as carriers of immunotherapeutic agents. Recently, chimeric virus-like particle vaccines have been developed to treat existing human papillomavirus-induced neoplasms.
Immunotherapy protocols using a variety of recombinant vectors and modified human papillomavirus proteins induce in-vitro T cell responses and may lead to tumor regression. Vaccine-induced in-vitro immune reactivity and clinical vaccine effects are often not well associated. Further analysis of ongoing human immunotherapy trials is awaited.
综述预防和治疗人乳头瘤病毒感染及相关疾病的新型免疫策略。同时讨论了动物模型系统和人体试验方案。
已开发出多种用于预防人乳头瘤病毒感染和治疗相关疾病的疫苗平台。含有乳头瘤病毒衣壳蛋白的病毒样颗粒构建体已被证明可预防人乳头瘤病毒感染。已制备出含有修饰的E6或E7蛋白的新型肽或蛋白质构建体、新型佐剂、融合蛋白(如免疫球蛋白G重链E7)或热休克蛋白作为治疗手段。此外,许多新的重组疫苗载体,如痘苗病毒、李斯特菌属、腺病毒、Semliki森林病毒载体等,已被开发作为免疫治疗剂的载体。最近,嵌合病毒样颗粒疫苗已被开发用于治疗现有的人乳头瘤病毒诱导的肿瘤。
使用多种重组载体和修饰的人乳头瘤病毒蛋白的免疫治疗方案可诱导体外T细胞反应,并可能导致肿瘤消退。疫苗诱导的体外免疫反应性和临床疫苗效果往往没有很好的相关性。有待对正在进行的人体免疫治疗试验进行进一步分析。