T LYMPHOCYTE RESPONSES TO HUMAN NEUROBLASTOMA

描述：(申请人摘要)神经母细胞瘤是最常见的 儿童颅外实体瘤。试图开发一种有效的 神经母细胞瘤的免疫治疗相对不成功。在……里面 尽管失败了，但令人信服的临床证据表明，这些 在某些情况下，肿瘤可以引发保护性免疫反应。 在其他癌症的有效免疫治疗方面取得了重大进展 用肿瘤特异性细胞毒性T淋巴细胞(CTL)定义肿瘤 能够刺激治疗性免疫反应的抗原。 与在小鼠体内容易产生神经母细胞瘤特异性CTL形成对比 模型，几个小组报告说很难产生人类CTL 对抗这种肿瘤。PI最近成功地产生了肿瘤- 几例神经母细胞瘤患者的特异性CTL。在这个项目中，他 建议使用这些CTL来推进这种肿瘤的免疫治疗。这个 该项目的具体目标是：1)使用这些CTL来测试 假设神经母细胞瘤肿瘤特异性抗原存在，以确定 这些抗原在分子水平上，并解释它们的表达 肿瘤免疫学和生物学背景下的模式；2)定义 诱导这些T细胞体外产生CTL的最佳条件 来自目前耐药肿瘤的细胞，并延长了 过继免疫疗法；以及3)检验已定义的假设 神经母细胞瘤肿瘤抗原可替代和超越天然肿瘤细胞 抗肿瘤CTL反应的产生。通过识别一个或多个 神经母细胞瘤肿瘤抗原及其最适培养条件的确定 产生抗肿瘤的CTL反应，这个项目将加速 这一重要的儿科癌症的免疫治疗的进展。

DESCRIPTION: (Applicant's Abstract) Neuroblastoma is the most common extra-cranial solid tumor in children. Attempts to develop an effective immunotherapy for neuroblastoma have been relatively unsuccessful. In spite of these failures, compelling clinical evidence suggests that these tumors can elicit a protective immune response under some circumstances. Significant progress toward useful immunotherapy of other cancers has been made using tumor-specific cytotoxic T lymphocytes (CTL) to define tumor antigens which are capable of stimulating a therapeutic immune response. In contrast to the ease of generating neuroblastoma-specific CTL in murine models, several groups have reported difficulty producing human CTL against this neoplasm. The PI has recently succeeded in generating tumor- specific CTL from several neuroblastoma patients. In this project he proposes to use these CTL to advance immunotherapy of this neoplasm. The specific aims of this project are: 1) to use these CTL to test the hypothesis that neuroblastoma tumor-specific antigens exist, to identify these antigens at the molecular levels, and to interpret their expression patterns in the context of tumor immunology and biology; 2) to define the optimal conditions for CTL generation in vitro in order to elicit these T cells from currently resistant tumors and extend the effectiveness of adoptive immunotherapy; and 3) to test the hypothesis the defined neuroblastoma tumor antigens can replace and surpass native tumor cells in the generation of anti-tumor CTL responses. By identifying one or more neuroblastoma tumor antigens and defining the optimal conditions for generating an anti-tumor CTL response, this project will accelerate the development of immunotherapy for this important pediatric cancer.