KLH-pulsed dendritic cells plus TNFerade in Pancreatic Cancer

KLH 脉冲树突状细胞加 TNFerade 在胰腺癌中的应用

• 批准号: 7488709
• 负责人: EMMANUEL E ZERVOS
• 金额: $ 24.56万
• 依托单位: EAST CAROLINA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-15 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7488709
• 关键词: Adenovirus Vector; Adoptive Immunotherapy; Adult; Adverse effects; Affect; Aftercare; Animal Model; Antigen-Presenting Cells; Antigens; Apoptosis; Apoptotic; Area; Autologous Dendritic Cells; Basic Science; Brachytherapy; CA-15-3 Antigen; Cancer Center; Cancer Etiology; Cells; Childhood; Class; Clinical; Clinical Research; Clinical Trials; Code; Combined Modality Therapy; Core Facility; Cytotoxic T-Lymphocytes; Dendritic Cell Therapy; Dendritic Cells; Diagnosis; Digestive System Disorders; Disease; Disease regression; Distant; Dose; Enrollment; Environment; Excision; Florida; Growth; Hemocyanin; Human; Hypersensitivity skin testing; Immune response; Immunologics; Immunotherapeutic agent; Incidence; Induction of Apoptosis; Infiltration; Injection of therapeutic agent; Institution; Keyhole Limpet Hemocyanin; Major Histocompatibility Complex; Malignant Neoplasms; Malignant neoplasm of gastrointestinal tract; Malignant neoplasm of pancreas; Measures; Methods; Necrosis; Operative Surgical Procedures; Outcome; Pancreas; Pancreatic Adenocarcinoma; Patients; Phase II Clinical Trials; Physiologic pulse; Primary Neoplasm; Progression-Free Survivals; Protocols documentation; Pulse taking; Purpose; Radiation; Rate; Reporting; Research Personnel; Safety; Serum; Solid Neoplasm; Spiral Computed Tomography; Staging; Standards of Weights and Measures; Survival Rate; Symptoms; TNF gene; Therapeutic; Time; Transcriptional Activation; Translational Research; Treatment Protocols; Tumor Antigens; Tumor Necrosis Factor-alpha; United States; Up-Regulation; X-Ray Computed Tomography; cone-beam computed tomography; design; human TNF protein; indexing; mortality; novel; pancreatic neoplasm; patient oriented; programs; response; tumor; vector

DESCRIPTION (provided by applicant): In the United States, approximately 30,000 people die of pancreatic cancer each year. Among cancers of the gastrointestinal tract, it is the third most common malignancy and the fifth leading cause of cancer-related mortality overall. The disease is difficult to diagnose in its early stages, and almost 90% of patients have incurable disease by the time they present with symptoms. The overall 5-year survival rate for this disease is less than 5%, so mortality rates approach incidence rates. The only treatment that offers a survival advantage is surgical resection. To date, no effective therapies exist for patients with inoperable disease (locally advanced or metastatic pancreatic cancer). This is a phase II clinical trial that combines two novel therapies for solid tumors in patients with inoperable pancreatic cancer--TNFerade to induce apoptosis and dendritic cell therapy to induce an immunlogic response. Each therapy has been shown to individually affect the growth of pancreatic adenocarcinoma and clinical outcomes in patients with this disease. The combination of these therapies has never been proposed or executed in this clinical setting, but animal models show a therapeutic synergy that leads to tumor regression and protection against subsequent challenge with the same tumor type. The long term and broad objectives of this project are to determine whether a lasting immune response can be induced in patients with pancreatic cancer using autologous dendritic cells pulsed with keyhole limpit hemocyanin after the induction of apoptosis in the primary tumors with an adenoviral vector coding for human tumor necrosis factor-alpha (TNFerade). The specific aims of this project are as follows: 1) To establish the feasability and safety of intratumoral injections of activated dendritic cells combined with TNFerade in the treatment of locally advanced / metastatic pancreatic cancer; 2) To determine the immunologic and anti-tumor effects of DC combined with TNFerade in patients with advanced pancreatic malignancy; 3) To determine the effect of TNFerade on the local microenvironment after injection and activation. Patients with inoperable tumors will be enrolled to receive the treatment protocol. The tumors will be evaluated for the degree of apoptosis, and the patients will be investigated for a systemic response to tumor associated antigens.

描述（由申请人提供）：在美国，每年约有30,000人死于胰腺癌。在胃肠道的癌症中，它是第三大最常见的恶性肿瘤，也是癌症相关死亡率的第五个主要原因。该疾病在早期很难诊断，并且在出现症状时，几乎90％的患者患有无法治愈的疾病。该疾病的总5年生存率小于5％，因此死亡率接近发生率。提供生存优势的唯一治疗方法是手术切除。迄今为止，对于无法手术疾病（局部晚期或转移性胰腺癌）的患者尚无有效的疗法。这是一项II期临床试验，结合了无法手术胰腺癌患者实体瘤的两种新型疗法 - 诱导凋亡和树突状细胞疗法诱导免疫反应。已显示每种疗法都会单独影响该疾病患者胰腺癌的生长和临床结局。在这种临床环境中，从未提出或执行这些疗法的结合，但是动物模型显示出一种治疗性协同作用，可导致肿瘤回归和防止随后对相同肿​​瘤类型的挑战。该项目的长期目标和广泛的目标是确定胰腺癌患者是否可以使用自动物limpit limpit limpit Hemocyanin脉动的胰腺癌患者诱导腺病毒载体编码人类肿瘤Necrosis Necrosis因子因子 - TNNPHA（TNNECRADE）的原发性肿瘤（TNE）。该项目的具体目的如下：1）确定活化树突状细胞的肿瘤内注射的可行性和安全性，并在治疗局部晚期 /转移性胰腺癌治疗中结合了TNFerade； 2）确定DC的免疫学和抗肿瘤作用与TNFerade结合了晚期胰腺恶性肿瘤的患者； 3）确定注射和激活后Tnferade对局部微环境的影响。无法接受肿瘤的患者接受治疗方案。将评估肿瘤的凋亡程度，并将研究患者对肿瘤相关抗原的全身反应。