Listeria Monocytogenes to Treat Hepatic Metastases

描述（由申请人提供）：2004年，预计约有1,368,060名美国人患癌症，563,700人预计死亡，每天超过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年治疗癌症的总费用为1895亿美元。许多癌症，如起源于消化系统的癌症，有很高的发展为肝转移的倾向，在许多病例中，发病和死亡的主要原因是肝转移。2004年美国消化系统癌症死亡人数预计将达到134840人。此外，其他类型的癌症，如呼吸系统癌、乳腺癌和皮肤癌也会发生肝转移。尽管进行了手术、放疗和化疗等积极的治疗，但41%的癌症患者最终还是会死于疾病。免疫疗法有可能为许多癌症提供另一种全身治疗方法。

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.