In Vivo Responses of DC Vaccines Presenting HLA Class I and II Restricted Tumor Epitopes Either by Peptide-pulsing or mRNA Transfection in Melanoma Patients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 64
- 试验地点
- 2
- 主要终点
- Immune response
研究概览
简要总结
Dendritic cells (DCs)are the most potent antigen-presenting cells of the immune system, as such they are able to direct the immune system specifically against cancer cells. Currently DCs are used in clinical vaccination studies and immunological and clinical responses have been observed. For inducing anti-tumor immunity, the DCs have to be loaded with tumor antigen (i.e. molecular structures that are presented by the tumor, that are recognized by the immune system). Currently most studies use tumor peptides (small protein fragments) for this purpose. This approach has several disadvantages: only patients with a certain HLA-type can be treated and the immune response that is induced by the vaccine is limited to the used peptides. These disadvantages do not exist when the DCs present antigen which is endogenously processed, for example after RNA transfection. For this reason we investigate the immunogenicity of DCs that are pulsed with peptides or transfected with mRNA encoding melanoma associated antigens in stage III and IV melanoma patients.
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
- •For both stage III and IV
- •Histological proof of cutaneous melanoma
- •Melanoma expressing both gp100 and tyrosinase, each in approximately 20% or more of cells by immunohistochemistry staining,
- •HLA type A2 and/or A3, with known HLA-DR4 expression,
- •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.
- •For Stage III only
- •Stage III melanoma according to the 2001 AJCC criteria.
- •Start of treatment within 2 months of lymph node dissection for melanoma stage III
- •For stage IV only
- •Stage IV melanoma according to the 2001 AJCC criteria. Limited tumor burden; LDH < 2x upper limit of normal
排除标准
- •For both stage III and IV
- •No autoimmune disorders, no concomitant use of immunosuppressive drugs,
- •no serious concomitant disease, no serious active infections, no other malignancy in the past 5 years with the exception of curatively treated carcinoma in-situ of the cervix/squamous cell carcinoma of the skin,
- •No known allergy to shell fish (contains KLH) are excluded.
- •No pregnancy or lactation,
- •For stage III only:
- •No signs or symptoms of distant metastases as defined by normal history, physical examination, chest X-ray and serum LDH.
- •No concomitant or previous systemic treatment for melanoma
- •For stage IV only:
- •No clinical signs of CNS metastases, in patients with a clinical suspicion of CNS metastases, a CT scan of the brain should be performed to exclude this.
- •No prior chemotherapy, immunotherapy, or radiotherapy within three months before planned vaccination is allowed.
结局指标
主要结局
Immune response
时间窗: first 10 years
次要结局
- Safety(first 10 years)