GM-CSF Enhanced Colorectal Cancer Tumor Vaccine Program

GM-CSF增强型结直肠癌肿瘤疫苗计划

• 批准号: 7477966
• 负责人: RICHARD D SCHULICK
• 金额: $ 14.01万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7477966
• 关键词: Adjuvant Therapy; Aftercare; Autologous; Autologous Tumor Cell; Cancer Vaccines; Cell Line; Cells; Cessation of life; Clinic; Clinical; Clinical Trials; Colon, Rectum; Colorectal; Colorectal Cancer; Development; Diagnosis; Disease; Disorder by Site; Distant Metastasis; Effectiveness; Elements; Excision; Granulocyte-Macrophage Colony-Stimulating Factor; Harvest; Hepatic; Human; Immune response; Immune system; Immunity; Immunologics; Immunotherapeutic agent; Immunotherapy; Laboratories; Lead; Lesion; Life; Liver; Malignant Neoplasms; Metastatic Neoplasm to the Liver; Microscopic; Modality; Modeling; Mus; Neoplasm Metastasis; No Evidence of Disease; Numbers; Patients; Phase I Clinical Trials; Phase II Clinical Trials; Population; Preparation; Protocols documentation; Radiosurgery; Research Proposals; Resectable; Resected; Residual state; Safety; Site; Standards of Weights and Measures; T-Lymphocyte; Testing; Time; Translating; Tumor Burden; United States; Vaccination; Vaccines; base; chemotherapy; neoplastic cell; novel therapeutics; paracrine; pre-clinical; programs; research study; tumor

DESCRIPTION (provided by applicant): In the United States cancers of the colon and rectum are the third most common site of new cases and deaths. There were an estimated 148,300 new cases and 56,600 deaths from the disease in 2002. All too often, the cancer has metastasized by the time of diagnosis, and the most common site of distant metastasis is the liver. One promising strategy is immunotherapy that harnesses the antitumor effect of the patient's own immune system. Tumor cells combined with the paracrine release of granulocyte-macrophage colony stimulating factor (GM-CSF) are highly effective in generating potent T cell dependent systemic immunity capable of curing mice of very small burdens of pre-established tumors. The long-term objective of this proposal is to build an immunotherapy program against colorectal cancer based on GM-CSF tumor cell vaccines, and to translate novel therapeutic immunotherapeutic approaches from the laboratory to the clinics. The specific aims of this research proposal are: Specific Aim 1: To study the elements of the immune response of mice that eliminate established hepatic metastases after treatment with GM-CSF augmented tumor cell vaccines and to study mechanisms of focusing a systemically generated immune response into the liver. Specific Aim 2: A) To develop standard operating protocols to dissociate tumor cells from human colorectal cancer metastases to the liver so that they may be successfully isolated, irradiated, and stored for vaccine preparation. B) To produce a clinical lot of GM-CSF-secreting bystander cells. Specific Aim 3: To conduct a phase I clinical trial to study the safety and feasibility of a vaccine approach against colorectal cancer that combines autologous irradiated tumor cells isolated from hepatic metastases combined with a bystander cell line that secretes GM-CSF.

描述（由申请人提供）：在美国，结肠癌和直肠癌是新发病例和死亡的第三大常见部位。 2002 年估计有 148,300 例新发病例，56,600 人死于该病。癌症在诊断时常常已经发生转移，最常见的远处转移部位是肝脏。 一种有前途的策略是利用患者自身免疫系统的抗肿瘤作用的免疫疗法。 肿瘤细胞与粒细胞-巨噬细胞集落刺激因子 (GM-CSF) 的旁分泌释放相结合，能够非常有效地产生强大的 T 细胞依赖性全身免疫，能够治愈预先形成的肿瘤负担非常小的小鼠。 该提案的长期目标是建立基于GM-CSF肿瘤细胞疫苗的结直肠癌免疫治疗计划，并将新型治疗性免疫治疗方法从实验室转化为临床。 本研究计划的具体目标是： 具体目标 1：研究消除已建立的小鼠免疫反应的要素 GM-CSF 增强肿瘤细胞疫苗治疗后的肝转移并进行研究 将系统产生的免疫反应集中到肝脏的机制。 具体目标 2：A) 开发标准操作方案以从人体中分离肿瘤细胞 结直肠癌转移至肝脏，以便可以成功地分离、照射和储存它们以用于疫苗制备。 B) 生产临床批次的分泌 GM-CSF 的旁观细胞。 具体目标3：进行I期临床试验，研究疫苗的安全性和可行性 结合从体内分离的自体辐射肿瘤细胞来对抗结直肠癌 肝转移瘤与分泌 GM-CSF 的旁观者细胞系相结合。

项目成果

Selective targeting of antitumor immune responses with engineered live-attenuated Listeria monocytogenes.

使用工程化的减毒活单核细胞增生李斯特菌选择性靶向抗肿瘤免疫反应。

• 发表时间: 2006-01-15
• 作者: Yoshimura, Kiyoshi;Jain, Ajay;Allen, Heather E;Laird, Lindsay S;Chia, Christina Y;Ravi, Sowmya;Brockstedt, Dirk G;Giedlin, Martin A;Bahjat, Keith S;Leong, Meredith L;Slansky, Jill E;Cook, David N;Dubensky, Thomas W;Pardoll, Drew M;Schulick
• 通讯作者: Schulick