A Phase II Study of Adoptive Immunotherapy Using Dendritic Cells Pulsed with Tumor Lysate in Patients with Hepatocellular Carcinoma
A Phase II Study of Adoptive Immunotherapy Using Dendritic Cells Pulsed with Tumor Lysate in Patients with Hepatocellular Carcinoma
复制标题
DOI：
10.1002/hep.22626
复制
发表时间：
2009-01-01
期刊：
影响因子：
13.5
通讯作者：
Adams, David H.
中科院分区：
文献类型：
--
作者：
Palmer, Daniel H.;Midgley, Rachel S.;Adams, David H.
这是一项II期临床试验，研究了用肝癌细胞系裂解物(HepG2)体外致敏的成熟自体树突状细胞(DC)静脉接种晚期肝细胞癌(HCC)患者的安全性和有效性。在体外研究中，肿瘤浸润性淋巴细胞能够裂解自体肿瘤细胞，这证明了肝癌是一个有吸引力的免疫治疗靶点。DC是最强大的抗原提呈细胞，具有摄取、处理和递呈肿瘤抗原给T细胞并刺激免疫反应的能力，从而为疫苗的开发提供了一个合理的平台。35名不适合根治性或局部区域治疗的晚期肝癌患者每隔3周接受最多6次DC疫苗接种。总共进行了134次DC输注，没有明显的毒性，也没有自身免疫的证据。对25名接受了至少三次疫苗注射的患者进行了临床反应评估。放射学确定的疾病控制率(部分缓解和稳定疾病相结合=3个月)为28%。在17名患者中，基线血清甲胎蛋白(AFP)为1,000 ng/ml；在其中4名患者中，其水平降至
This is a phase II clinical trial investigating the safety and efficacy of intravenous vaccination with mature autologous dendritic cells (DCs) pulsed ex vivo with a liver tumor cell line lysate (HepG2) in patients with advanced hepatocellular carcinoma (HCC). HCC is an attractive target for immunotherapy as evidenced by an active recruitment of tumor-infiltrating lymphocytes that are capable of lysing autologous tumor cells in ex vivo studies. DCs are the most potent antigen-presenting cells, with the capacity to take up, process, and present tumor antigens to T cells and stimulate an immune response, thus providing a rational platform for vaccine development. Thirty-five patients with advanced HCC and not suitable for radical or loco-regional therapies received a maximum of six DC vaccinations each at 3-week intervals. In total, 134 DC infusions were administered with no significant toxicity and no evidence of autoimmunity. Twenty-five patients who received at least three vaccine infusions were assessed clinically for response. The radiologically determined disease control rate (combined partial response and stable disease >= 3 months) was 28%. In 17 patients the baseline serum alpha-fetoprotein (AFP) was >= 1,000 ng/ml; in four of these patients, it fell to