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.'

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此，可以在其他清晰的条目中表示。列出的机构是 对于中心，这不一定是调查员的机构。 膀胱癌今年将杀死12,000人。 近30-35％的患者患有肌肉侵入性疾病。 标准疗法是根治性的膀胱切除术，但是40-50％的患者将复发。 在这种情况下，新辅助化疗没有明显的生存益处，因此需要新的治疗策略。 树突状细胞（DC）是刺激原发性和继发性免疫反应的高效抗原呈现细胞。临床前的体外和动物数据表明，富集的直流可以从外周血中收获，并在存在细胞因子的情况下培养以增强直流功能。 使用肿瘤裂解物或抗原肽培养，肿瘤特异性表现会导致T细胞反应增强，并在动物和人类中产生抗肿瘤作用。 来自各种晚期成人和小儿肿瘤中的I期试验的数据也表明，对施用皮内树突状细胞疫苗接种的毒性最少。 该提议的假设是，可以使用肿瘤内注射暴露于肿瘤抗原，将DC用于免疫系统膀胱肿瘤特异性抗原。 该阶段I试验将概述活化和KLH脉冲自体树突状细胞的肿瘤内注射的安全性。 在这方面，将采用树突状细胞给药的剂量升级。 我们将使用柔性膀胱镜检查在门诊环境中使用柔性膀胱镜检查来研究腹腔内细胞注射的可行性。 此外，将通过免疫和免疫组织化学分析探索与DC疫苗接种相关的免疫学和抗肿瘤反应。 这项研究的具体目的包括以下内容： 1。确定每周的肿瘤内给药，自体内活化的KLH脉冲树突状细胞疫苗在局部晚期膀胱癌患者中的安全性。 2。概述串行肿瘤内直流注射的可行性。 3。评估对激活的KLH脉冲DC治疗的免疫学反应。