Clinical and immunologic responses to active specific cancer vaccines in human colorectal cancer
Clinical and immunologic responses to active specific cancer vaccines in human colorectal cancer
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DOI：
10.1158/1078-0432.ccr-05-2788
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发表时间：
2006-05-15
影响因子：
11.5
通讯作者：
Thiel, Eckhard
中科院分区：
文献类型：
--
作者：
Nagorsen, Dirk;Thiel, Eckhard
结直肠癌是一种常见的恶性疾病，尽管取得了一些进展，但仍需要改进治疗方案。几项临床研究已经使用了主动特异性免疫疗法（即，接种疫苗）在结直肠癌中的作用。然而，文献仍然缺乏对这种方法在晚期结直肠癌中的综合荟萃分析。我们对临床研究进行了荟萃分析，以评估结直肠癌患者对主动特异性免疫治疗的客观临床和免疫学反应。我们对Medline和Web of Science进行了搜索，手动审查了文献，并咨询了专家。纳入研究的标准是结肠直肠癌患者、诱导针对癌症或癌症抗原的应答的主动特异性免疫疗法、可评估的肿瘤负荷（即，晚期或转移性结直肠癌），以及患者、疾病和反应的精确分类。根据WHO标准评估缓解率。主要终点为客观临床应答率和免疫应答率。次要终点是与疫苗接种途径和疫苗类型相关的免疫和临床应答的分布。32项I/II期研究报告了527例晚期或转移性结直肠癌患者，符合所有入选标准。汇总分析显示，接受多种物质（例如，自体肿瘤细胞、肽疫苗、树突细胞、独特型抗体和基于病毒的疫苗）。59%的病例报告了体液免疫应答，44%的病例报告了细胞免疫应答。混合或轻微缓解和疾病稳定分别在1.9%和8.3%的结直肠癌患者中描述。临床试验的汇总结果显示，目前可用于晚期结直肠癌的主动特异性免疫程序的临床应答率非常低，为0%。大约一半的患者描述了免疫应答诱导。
Colorectal cancer is a common malignant disease, which, despite some progress, still requires improved therapeutic options. Several clinical studies have used active specific immunotherapy (i.e., vaccination) in colorectal cancer. However, the literature still lacks a comprehensive meta-analysis of this approach in advanced colorectal cancer. We did a systematic review with a meta-analysis of clinical studies to evaluate the objective clinical and immunologic response to active specific immunotherapy in patients with colorectal cancer. We conducted a search of Medline and the Web of Science, manually reviewed the literature, and consulted with experts. Criteria for including studies were colorectal cancer patients, active specific immunotherapy to induce a response directed against cancer or cancer antigens, an evaluable tumor burden (i.e., advanced or metastatic colorectal cancer), and precise classification of the patient, disease, and response. Response rates were assessed according to WHO criteria. Primary end points were the objective clinical response rate and the rate of immunologic responses. The secondary end point was the distribution of immune and clinical responses in relation to the route of vaccination and the type of vaccine. Thirty-two phase I/II studies reporting on 527 patients with advanced or metastatic colorectal cancer met all inclusion criteria. Pooled analysis showed an overall response rate (complete response + partial response) of 0.9% for advanced/metastatic colorectal cancer patients who underwent active specific immunization with a broad variety of substances (e.g., autologous tumor cells, peptide vaccine, dendritic cells, idiotypic antibody, and virus-based vaccine). Humoral immune responses were reported in 59%, and cellular ones were reported in 44% of the cases. Mixed or minor responses and disease stabilization are described in 1.9% and 8.3% of colorectal cancer patients, respectively. Pooled results of clinical trials reveal a very weak clinical response rate of 0% for active specific immunization procedures currently available for advanced colorectal cancer. Immune response induction is described in approximately half the patients.