ADMIN OF AUTOLOGOUS DENDRITIC CELLS ACTIVATED BY GM-CSF & IL-4 AS TUMOR VACCINE

GM-CSF 激活的自体树突状细胞的管理

• 批准号: 7603704
• 负责人: CHERYL T. LEE
• 金额: $ 0.14万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7603704
• 关键词: Adult; Animals; Antigen-Presenting Cells; Antigens; Antitumor Response; Autologous; Autologous Dendritic Cells; Bladder Neoplasm; Cancer Patient; Cancer Vaccines; Cell physiology; Cells; Computer Retrieval of Information on Scientific Projects Database; Cystoscopy; Data; Dendritic Cell Therapy; Dendritic Cell Vaccine; Dendritic Cells; Disease; Dose; Exposure to; Feasibility Studies; Funding; Grant; Harvest; Human; Immune system; Immunologic Memory; Immunologics; In Vitro; Injection of therapeutic agent; Institution; Interleukin-4; Invasive; Malignant neoplasm of urinary bladder; Muscle; Neoadjuvant Therapy; Outpatients; Patients; Pediatric Neoplasm; Peptides; Phase I Clinical Trials; Physiologic pulse; Pulse taking; Radical Cystectomy; Research; Research Personnel; Resources; Safety; Source; Standards of Weights and Measures; T-Lymphocyte; Toxic effect; Tumor Antigens; United States National Institutes of Health; Vaccination; animal data; chemotherapy; cytokine; intravesical; killings; novel; peripheral blood; pre-clinical; response; tumor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Bladder cancer will kill 12,000 people this year. Nearly 30-35% of patients present with muscle invasive disease. The standard therapy is radical cystectomy, however, 40-50% of patients will recur. Neoadjuvant chemotherapy offers no clear survival benefit in this setting, so novel treatment strategies are necessary. Dendritic cells (DC) are highly potent antigen presenting cells that stimulate primary and secondary immune responses. Preclinical in vitro and animal data have shown that enriched DC can be harvested from peripheral blood and cultured in the presence of cytokines to enhance DC function. Using tumor lysates or antigen peptide culture, tumor-specific presentation can result in a heightened T-cell response and an antitumor effect in animals and in humans. Data from ongoing Phase I trials in a variety of advanced adult and pediatric tumors has also demonstrated a minimal observable toxicity with the administration of intradermal dendritic cell vaccination. The hypothesis of this proposal is that DC can be utilized to present bladder tumor specific antigens to the immune system through exposure to tumor antigens using intratumoral injection. This Phase I trial will outline the safety profile of intratumoral injection of activated and KLH-pulsed autologous dendritic cells. In this regard, a dose escalation of dendritic cell administration will be employed. We will study the feasibility of intravesical intratumoral cell injection using flexible cystoscopy for visually directed administration in the outpatient setting. Further, immunologic and antitumor responses related to DC vaccination will be explored through immunologic and immunohistochemical analyses. The specific aims of this study include the following: 1. To determine the safety of weekly intratumoral administration of autologous, activated, KLH-pulsed dendritic cell vaccines in locally advanced bladder cancer patients. 2. To outline the feasibility of serial intratumoral DC injections. 3. To evaluate the immunologic response to activated KLH-pulsed DC therapy.'

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 膀胱癌今年将导致12,000人死亡。 近30-35%的患者存在肌肉浸润性疾病。 标准治疗是根治性膀胱癌，然而，40-50%的患者会复发。 新辅助化疗在这种情况下没有明显的生存益处，因此新的治疗策略是必要的。 树突状细胞（DC）是一种高效的抗原提呈细胞，可刺激原发性和继发性免疫应答。临床前体外和动物数据表明，富集的DC可以从外周血中收获，并在细胞因子的存在下培养以增强DC功能。 使用肿瘤裂解物或抗原肽培养物，肿瘤特异性呈递可在动物和人类中导致增强的T细胞应答和抗肿瘤作用。 在多种晚期成人和儿童肿瘤中进行的I期试验的数据也证明了皮内树突状细胞疫苗接种的最小可观察毒性。 该建议的假设是，DC可用于通过使用肿瘤内注射暴露于肿瘤抗原而将膀胱肿瘤特异性抗原呈递给免疫系统。 这项I期试验将概述肿瘤内注射活化和KLH脉冲的自体树突状细胞的安全性。 在这方面，将采用树突细胞施用的剂量递增。 我们将研究在门诊环境中使用柔性膀胱镜进行膀胱内肿瘤内细胞注射的可行性，以进行视觉指导给药。 此外，免疫学和免疫组织化学分析将探讨与DC疫苗接种相关的免疫和抗肿瘤反应。 这项研究的具体目标包括： 1.确定局部晚期膀胱癌患者每周瘤内注射自体活化KLH脉冲树突状细胞疫苗的安全性。 2.概述连续瘤内DC注射的可行性。 3.目的：评价活化KLH脉冲DC治疗的免疫应答。'