T CELL FOCUSED CANCER VACCINES IN MURINE TUMOR MODELS

描述：(申请者摘要)六分之一的人会死于癌症。 免疫的全身性、回忆能力和精湛的特异性 该系统使免疫治疗成为癌症治疗的一个诱人的前景。 肝细胞癌、宫颈癌、各种白血病和 淋巴瘤都被认为是病毒引起的。病毒编码的肿瘤特异性 抗原使病毒相关肿瘤成为免疫治疗的有力候选者。 最近的研究描述了类猴病毒40(SV40)的存在 基因序列和蛋白质(特别是大肿瘤抗原：SV40 Tag)在骨肉瘤、胶质母细胞瘤、室管膜瘤和恶性肿瘤中的表达 胸膜间皮瘤(MPM)，显示SV40与某些 人类的恶性肿瘤。促进人类临床的发展 SV40相关人类恶性肿瘤的免疫治疗方案 拟议的研究将使用SV40小鼠肿瘤系统来评估 CTL转移疗法和基于多肽的疫苗的有效性 靶向体内表达肿瘤的SV40标签的免疫应答。简单地说， SV40标签特异性CTL将通过免疫Balb/c小鼠产生 SV40标签基因的构建及其表位特异性的研究 选择代表潜在CTL的H-2d限制性合成肽 SV40标签上的表位。这些CTL将被用来检查 过继转移的T细胞对肿瘤的保护作用 同基因小鼠。此外，还将对选定的合成肽进行检查 在体内主动诱导保护性肿瘤免疫的能力。 完成这项研究将提供有价值的信息，积极 用SV40标签表位特异性诱导肿瘤破坏性免疫 体内CTL。此外，使用小鼠SV40产生的信息 肿瘤模型将加快试剂和临床试验的发展 设计用于检查SV40相关的SV40标签特异性免疫疗法 人类的恶性肿瘤。

DESCRIPTION: (Applicant's Abstract) One in six people will die of cancer. the systemic nature, recall ability and exquisite specificity of the immune system makes immunotherapy an attractive prospect for cancer treatment. Hepatocellular carcinoma, cervical carcinoma, various leukemias and lymphomas all have proposed viral etiologies. Viral encoded tumor specific antigens make viral associated tumors strong candidates for immunotherapy. Recent studies have described the presence of simian virus 40 (SV40)-like gene sequences and proteins (specifically the large tumor antigen: SV40 Tag) in human osteosarcomas, glioblastomas, ependymomas and malignant pleural mesotheliomas (MPM), demonstrating SV40 association with certain human malignancies. To facilitate the development of human clinical protocols for the immunotherapy of SV40 associated human malignancies, the proposed study will employ an SV40 murine tumor system to evaluate the efficacy of CTL transfer therapies and peptide based vaccines designed to target an immune response to SV40 Tag expressing tumors in vivo. Briefly, SV40 Tag specific CTL will be generated by immunization of Balb/c mice with SV40 Tag gene constructs and the epitope specificity determined by using selected H-2d restricted synthetic peptides representing potential CTL epitopes on SV40 Tag. These CTL will be utilized to examine the ability of adoptively transferred T cells to protect against tumor challenge in syngeneic mice. Further, selected synthetic peptides will be examined for the ability to actively induce protective tumor immunity in vivo. Completion of this study will provide valuable information on the active induction of tumor destructive immunity involving SV40 Tag-epitope specific CTL in vivo. Moreover, the information generated using the murine SV40 tumor model will expedite the development of reagents and clinical trials designed to examine SV40 Tag specific immunotherapies for SV40 associated human malignancies.