Induction of Specific T Cell Responses in Colorectal Cancer Patients With Liver Metastases Upon Vaccination With Autologous Dendritic Cells Pulsed With CEA-peptide or Electroporated With CEA-RNA: Evaluation of in Vivo Immune Response.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- immunological response against carcinoembryonic antigen and the control protein KLH
研究概览
简要总结
Dendritic cells (DCs) are the professional antigen-presenting cells of the immune system. As such they are currently used in clinical vaccination protocols in cancer patients. We evaluate the ability of mature DCs pulsed with carcinoembryonic antigen (CEA)-peptide (arm A) or electroporated with CEA-mRNA (arm B) to induce CEA-specific T cell responses in patients with resectable liver metastases from colorectal cancer. To evaluate immune responses, CEA-specific T cell reactivity is monitored in peripheral blood, resected abdominal lymph nodes, tumor tissue and biopsies of vaccination sites and post-treatment DTH skin tests. Patients are vaccinated intradermally and intravenously with CEA-peptide pulsed mature DCs three times prior to resection of liver metastases. In 2007 a side-study has been added (arm C), in which patients with stage III or high-risk stage II colorectal cancer that are amenable for standard adjuvant oxaliplatin/capecitabine therapy are vaccinated with CEApeptide-pulsed DCs. Also in this group, safety and immune responses in peripheral blood and the DTH-skin test are the primary endpoints. Results are compared with the results obtained in arm A.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histological documented evidence of colorectal cancer.
- •Primary tumor surgically removed, recurrence(s) in the liver.
- •Planned surgical excision of liver metastases.
- •HLA-A2.1 phenotype according to lymphocyte HLA typing.
- •Expression of CEA on primary tumor.
- •ECOG performance status 0-1, life expectancy > 3 months.
- •Age 18-75 years.
- •WBC > 3.0 x 109/l, lymphocytes > 0.8 x 109/l, platelets > 100 x 109/l, serum creatinine < 150 μmol/l, serum bilirubin < 25 μmol/l.
- •Expected adequacy of follow-up.
- •Written informed consent.
排除标准
- •Clinical signs of extra hepatic metastases, in patients with a clinical suspicion of other metastases diagnostic tests should be performed to exclude this.
- •Prior chemotherapy, immunotherapy, or radiotherapy within three months before planned surgical excision is allowed.
- •A history of myocardial infarction, angina pectoris, cardiac arrhythmias, cerebrovascular accidents, transient ischemic attacks or severe hypertension (exclusion criteria for autologous blood donation)
- •Concomitant use of corticosteroids or other immunosuppressive agents.
- •A history of any second malignancy in the past five years excluding adequately treated basal carcinoma of skin or carcinoma in situ of cervix.
- •Serious concomitant disease, active infections. Specifically, patients with autoimmune disease or organ allografts and patients with a history of HBsAg or HIV are excluded.
- •A known allergy to shell fish.
- •Pregnant or lactating women.
- •For arm C (side-study)
- •inclusion criteria:
- •histological proof of colorectal cancer
- •HLA-A0201 positive
- •stage III (T1-4N1-2M0) cancer or high risk stage II (T4 and/or poor differentiation in histology and/or perforation and/or obstruction and/or venous invasion and/or histological analysis of ≤10 lymph nodes)
- •≤ 8 weeks since surgical resection of primary colorectal tumor
- •Age 18-75 years
- •WHO performance 0-1 (Karnofsky 100-70%)
- •WBC ≥ 3.0x109/l
- •Platelets ≥ 100x109/l
- •Hb ≥ 6 mmol/l
- •Total bilirubin ≤ 2x UNL
- •ASAT and ALAT ≤ 3x UNL
- •Serum creatinine ≤ 1.5 x UNL
- •Expected adequacy of follow-up
- •Signed written informed consent
- •exclusion criteria
- •A history of second malignancy within the last 5 years. Adequately treated basal carcino¬ma of skin or carcinoma in situ of cervix is acceptable within this period
- •Serious concomitant disease. Autoimmune disease or organ grafts.
- •Other serious concomitant diseases preventing the safe administration of study drugs or likely to interfere with the study assessments.
- •A known allergy to shell fish (contains KLH)
- •Pregnant or lactating women
结局指标
主要结局
immunological response against carcinoembryonic antigen and the control protein KLH
时间窗: During the study
Toxicity
时间窗: During the study
次要结局
未报告次要终点