VLP VACCINES AGAINST HPV INDUCED TUMORS

描述（改编自研究者摘要）：总体目标 该项目旨在确定乳头瘤病毒样颗粒的疗效， （VLP）作为人宫颈癌的预防性和治疗性疫苗。 初步结果中描述的详细实验模型 涉及通过注射C3细胞（鼠胚胎细胞）诱导肿瘤 用全长HPV 16病毒DNA与活化的ras一起转化） 同基因免疫小鼠。 该系统已经过验证， 鉴定诱导抗肿瘤CTL应答的HPV 16 E7的表位。 识别该表位的CTL克隆可防止过继免疫中的肿瘤形成。 转移实验 该模型将被用于测试VLP的效果 免疫对抗肿瘤免疫的产生。 这些研究 与由以下原因引起的人宫颈癌的疫苗接种有关： HPPV 16感染。 主要研究者还确定了HPV 16 E6和 由人类HLA-A等位基因识别的E7肽将促进 将疫苗策略应用于人类。 为了实现这一目标， 调查将对人类。 为了实现这一目标， 拟议的调查还将评估VLPs诱导 HLA转基因小鼠中HLA限制性T细胞反应，以及通过在 人外周血细胞的体外免疫。 p

DESCRIPTION (Adapted from the Investigator's Abstract): The overall aim of this project is to determine the efficacy of papillomavirus-like particles (VLPs) as preventative and therapeutic vaccines fro human cervical cancer. The detailed experimental model described in the preliminary results involves the induction of tumors by injecting C3 cells (murine embryo cells transformed with full length HPV16 viral DNA together with activated ras) into syngeneic immunocompetent mice. The system has been validated by identifying an epitope of HPV16 E7 that induces an anti-tumor CTL response. A CTL clone recognizing this epitope prevents tumor formation in adoptive transfer experiments. This model will be used to test the effects of VLP immunization on the generation of anti-tumor immunity. These studies are relevant to the vaccination of human cervical carinomas that result from HPPV16 infection. The principal investigator also identified HPV16 E6 and E7 peptides recognized by human HLA-A allels that will facilitate the application of vaccine strategy to humans. In pursuit of this goal, the proposed investigations will to humans. In pursuit of this goal, the proposed investigations will also assess the ability of VLPs to induce an HLA restricted T cell response in HLA transgenic mice, as well as by in vitro immunization of human peripheral blood cells. p