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(申请人提供)：在美国，每年约有30,000人死于胰腺癌。在胃肠道癌症中，它是第三种最常见的恶性肿瘤，也是与癌症相关的总死亡率的第五大原因。这种疾病在早期阶段很难诊断，几乎90%的患者在出现症状时已经患有不治之症。这种疾病的总体5年存活率不到5%，因此死亡率接近发病率。唯一提供生存优势的治疗方法是手术切除。到目前为止，还没有有效的治疗方法来治疗不能手术的疾病(局部晚期或转移性胰腺癌)。这是一项II期临床试验，结合了两种治疗无法手术的胰腺癌患者实体肿瘤的新疗法--TNFerade诱导细胞凋亡和树突状细胞疗法诱导免疫反应。每种治疗方法都已被证明单独影响胰腺癌的生长和这种疾病患者的临床结果。这些疗法的组合从未在这种临床环境中被提出或执行，但动物模型显示了一种治疗协同作用，导致肿瘤消退并保护其免受相同肿瘤类型的后续挑战。这个项目的长期和广泛的目标是确定在编码人肿瘤坏死因子-α(TNADE)的腺病毒载体诱导原发肿瘤细胞凋亡后，用锁孔Limpit血蓝蛋白冲击的自体树突状细胞能否在胰腺癌患者中诱导持久的免疫应答。本项目的具体目标如下：1)确定活化的树突状细胞联合TNFerade瘤内注射治疗局部晚期/转移性胰腺癌的可行性和安全性；2)确定DC联合TNFerade对晚期胰腺癌患者的免疫学和抗肿瘤作用；3)确定TNFerade注射和激活后对局部微环境的影响。无法手术的肿瘤患者将被纳入接受治疗方案。将评估肿瘤的凋亡程度，并调查患者对肿瘤相关抗原的全身反应。