Listeria Monocytogenes to Treat Hepatic Metastases

单核细胞增生李斯特菌治疗肝转移

• 批准号: 6988218
• 负责人: RICHARD D SCHULICK
• 金额: $ 32.19万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6988218
• 关键词: Listeria; Listeria infections; T lymphocyte; attenuated microorganism; colony stimulating factor; dendritic cells; flow cytometry; genetic strain; genetically modified animals; inflammation; laboratory mouse; leukocyte activation /transformation; liver neoplasms; metastasis; neoplasm /cancer immunotherapy; neoplasm /cancer vaccine; nonhuman therapy evaluation; tumor antigens; vaccine development; vaccine evaluation; Listeria; Listeria infections; T lymphocyte; attenuated microorganism; colony stimulating factor; dendritic cells; flow cytometry; genetic strain; genetically modified animals; inflammation; laboratory mouse; leukocyte activation /transformation; liver neoplasms; metastasis; neoplasm /cancer immunotherapy; neoplasm /cancer vaccine; nonhuman therapy evaluation; tumor antigens; vaccine development; vaccine evaluation

DESCRIPTION (provided by applicant): In 2004, about 1,368,060 Americans were expected to develop cancer and 563,700 were expected to die, more than 1,500 people a day. Cancer is the second leading cause of death in the US, exceeded only by heart disease. In the US, 1 of every 4 deaths is from cancer. The National Institutes of Health estimate overall costs for cancer in the year 2003 at $189.5 billion. [1] Many cancers such as those originating in the digestive system have a very high propensity to develop hepatic metastases and the primary cause of morbidity and mortality in many cases is from the liver metastases. Digestive system cancer deaths are expected to account for 134,840 deaths in the US in 2004. Additionally, other cancer types such as respiratory system, breast, and skin cancers also develop hepatic metastases. Despite aggressive treatments with surgery, radiation, and chemotherapy, 41% of patients diagnosed with cancer will succumb to their disease. Immunotherapy has the potential to provide an alternative systemic treatment for many cancers. The specific aims of this research proposal are: Specific Aim 1: Define the mechanisms by which GM-CSF secreting tumor vaccines and infection with attenuated Listeria strains eliminate metastatic disease from the liver. Specific Aim 2: Identify an optimally attenuated strain of Listeria that has strong efficacy at targeting an immune response to the liver and that has low toxicity. Specific Aim 3: Use attenuated Listeria strains that have been genetically engineered to express relevant tumor antigens to further enhance the targeted immune response. Specific Aim 4: Define the role of dendritic cells in the priming and targeting of the immune response.

描述（由申请人提供）：2004年，预计约有1,368,060名美国人患癌症，预计有563,700人死亡，每天有1,500多人。癌症是美国的第二大死亡原因，仅因心脏病而超过。在美国，每4例死亡中有1人来自癌症。美国国立卫生研究院估计癌症在2003年的总体成本为1895亿美元。 [1]许多起源于消化系统的癌症具有很高的发展肝转移的倾向，并且在许多情况下，发病率和死亡率的主要原因是肝转移。消化系统癌症的死亡预计将在2004年在美国造成134,840例死亡。此外，其他癌症类型（例如呼吸系统，乳腺癌和皮肤癌）也会发展出肝转移。尽管对手术，放射线和化学疗法进行了积极的治疗，但有41％的被诊断患有癌症的患者会屈服于他们的疾病。免疫疗法有可能为许多癌症提供替代的系统治疗方法。 该研究建议的具体目的是： 具体目标1：定义GM-CSF分泌肿瘤疫苗并用减毒李斯特菌菌株感染的机制，从而消除了肝脏的转移性疾病。 具体目标2：确定最佳减弱的李斯特菌菌株，该菌株在靶向对肝脏的免疫反应且毒性低方面具有很强的功效。 特定目的3：使用经过基因工程以表达相关肿瘤抗原的减毒李斯特菌菌株，以进一步增强靶向免疫反应。 特定目标4：定义树突状细胞在免疫反应的启动和靶向中的作用。