Listeria Monocytogenes to Treat Hepatic Metastases

单核细胞增生李斯特菌治疗肝转移

• 批准号: 7590470
• 负责人: RICHARD D SCHULICK
• 金额: $ 30.71万
• 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 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7590470
• 关键词: Accounting; American; Animal Model; Attenuated; Breast; Cancer Vaccines; Cause of Death; Cells; Cessation of life; Collaborations; Colony-Stimulating Factors; Consultations; Dendritic Cells; Diagnosis; Digestive System Cancer; Disease; Engineering; Granulocyte-Macrophage Colony-Stimulating Factor; Heart Diseases; Immune; Immune response; Immune system; Immunity; Immunotherapy; Infection; Inflammation; Laboratories; Listeria; Listeria monocytogenes; Liver; Liver diseases; Malignant Neoplasms; Metastatic Neoplasm to the Liver; Modeling; Morbidity - disease rate; Mus; Organ; Patients; Population; Radiosurgery; Research Proposals; Respiratory System; Role; Skin Cancer; T-Lymphocyte; Testing; Time; Tissues; Toxic effect; Tumor Antigens; United States National Institutes of Health; Vaccination; Virulence Factors; cancer cell; cancer type; chemotherapy; cost; gastrointestinal system; mortality; neoplastic cell; paracrine; research study; response; tumor

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，预计将有约 1,368,060 名美国人罹患癌症，预计将有 563,700 人死亡，即每天死亡人数超过 1,500 人。癌症是美国第二大死因，仅次于心脏病。在美国，每 4 例死亡中就有 1 例死于癌症。美国国立卫生研究院估计 2003 年癌症总成本为 1,895 亿美元。 [1] 许多癌症，例如起源于消化系统的癌症，具有非常高的发生肝转移的倾向，并且在许多情况下，发病和死亡的主要原因是肝转移。 2004 年，美国因消化系统癌症死亡的人数预计为 134,840 人。此外，呼吸系统癌、乳腺癌和皮肤癌等其他类型的癌症也会发生肝转移。尽管采取了手术、放疗和化疗等积极治疗方法，但 41% 的癌症患者仍会死于疾病。免疫疗法有可能为许多癌症提供替代的全身治疗。 本研究计划的具体目标是： 具体目标 1：明确分泌肿瘤疫苗的 GM-CSF 和减毒李斯特菌菌株感染消除肝脏转移性疾病的机制。 具体目标 2：鉴定一种最佳减毒李斯特菌菌株，该菌株在针对肝脏的免疫反应方面具有强大的功效，并且毒性较低。 具体目标3：使用经过基因工程改造表达相关肿瘤抗原的减毒李斯特菌菌株，进一步增强靶向免疫反应。 具体目标 4：定义树突状细胞在启动和靶向免疫反应中的作用。