VLP VACCINES AGAINST HPV INDUCED TUMORS

描述(改编自《调查员摘要》)：总体目标 该项目是为了确定乳头瘤病毒样颗粒的疗效。 (VLP)作为预防和治疗人类宫颈癌的疫苗。 初步结果中描述的详细实验模型 通过注射C3细胞(小鼠胚胎细胞)诱导肿瘤 用全长HPV16病毒DNA与激活的ras一起转化) 变成具有同基因免疫能力的小鼠。该系统已通过以下验证 鉴定可诱导抗肿瘤CTL反应的HPV16E7表位。 识别该表位的CTL克隆可预防过继肿瘤的形成 传递实验。该模型将被用来检验VLP的效果 免疫就产生了抗肿瘤免疫。这些研究是 与接种由以下原因引起的人宫颈癌有关 HPPV16感染。首席调查员还发现了HPV16E6和 人类HLA-A等位基因识别的E7多肽将促进 疫苗策略在人类中的应用。为了追求这一目标， 拟议的调查将对人类产生影响。为了追求这一目标， 拟议的调查还将评估VLP是否有能力诱导 人类白细胞抗原限制了人类白细胞抗原转基因小鼠的T细胞反应 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