Clinical and immunological evaluation of anti-apoptosis protein, survivin-derived peptide vaccine in phase I clinical study for patients with advanced or recurrent breast cancer.
Clinical and immunological evaluation of anti-apoptosis protein, survivin-derived peptide vaccine in phase I clinical study for patients with advanced or recurrent breast cancer.
复制标题
DOI：
10.1186/1479-5876-6-24
复制
发表时间：
2008-05-10
影响因子：
7.4
通讯作者：
Hirata K
中科院分区：
文献类型：
--
作者：
Tsuruma T;Iwayama Y;Ohmura T;Katsuramaki T;Hata F;Furuhata T;Yamaguchi K;Kimura Y;Torigoe T;Toyota N;Yagihashi A;Hirohashi Y;Asanuma H;Shimozawa K;Okazaki M;Mizushima Y;Nomura N;Sato N;Hirata K
我们以前报道过Survivin-2B是Survivin的一个剪接变异体，在各种类型的肿瘤中都有表达，Survivin-2B多肽可能作为一种有效的免疫原性癌症疫苗。本研究的目的是在I期临床研究中检测Survivin-2B多肽对晚期或复发乳腺癌患者的毒性，并对其进行临床和免疫学评估。我们设置了两个协议。在第一方案中，10例患者单独接种剂量递增的Survivin-2B多肽(0.1-1.0 mg)，每2周4次。方案二：4例患者接种该多肽，每次1.0 mg，与IFA混合，每2周4次。在第一个方案中，接种期间或接种后没有观察到不良事件。在第二个方案中，两名患者在注射部位有硬结。一名患者出现全身不适(1级)，另一名患者出现全身不适(1级)和发热(1级)。所有患者对多肽疫苗的耐受性良好。在第一个方案中，8名患者肿瘤标志物水平升高，1名患者略有下降，1名患者在本临床试验期间处于正常范围。在肿瘤大小方面，两名患者被认为是病情稳定(SD)。免疫学方面，在10名患者中，有3名(30%)检测到多肽特异性CTL频率增加。在第二个方案中，所有4名患者(100%)都检测到多肽特异性CTL频率的增加，尽管没有显著的临床有益反应。ELISPOT分析显示2例患者有多肽特异性的干扰素-γ反应，其中四聚体染色的多肽特异性CTL频率在两种方案中都增加了。这项I期临床研究显示，Survivin-2B多肽疫苗耐受性良好。与单独接种Survivin-2B多肽相比，联合IFA接种Survivin-2B多肽能更有效地增加多肽特异性CTL的频率，尽管两者都不能诱导有效的临床反应。综上所述，在Survivin-2B多肽与IFA混合免疫的基础上，加入另一种有效佐剂如细胞因子、热休克蛋白等，可能会引起更好的免疫学和临床反应。
We previously reported that survivin-2B, a splicing variant of survivin, was expressed in various types of tumors and that survivin-2B peptide might serve as a potent immunogenic cancer vaccine. The objective of this study was to examine the toxicity of and to clinically and immunologically evaluate survivin-2B peptide in a phase I clinical study for patients with advanced or recurrent breast cancer. We set up two protocols. In the first protocol, 10 patients were vaccinated with escalating doses (0.1–1.0 mg) of survivin-2B peptide alone 4 times every 2 weeks. In the second protocol, 4 patients were vaccinated with the peptide at a dose of 1.0 mg mixed with IFA 4 times every 2 weeks. In the first protocol, no adverse events were observed during or after vaccination. In the second protocol, two patients had induration at the injection site. One patient had general malaise (grade 1), and another had general malaise (grade 1) and fever (grade 1). Peptide vaccination was well tolerated in all patients. In the first protocol, tumor marker levels increased in 8 patients, slightly decreased in 1 patient and were within the normal range during this clinical trial in 1 patient. With regard to tumor size, two patients were considered to have stable disease (SD). Immunologically, in 3 of the 10 patients (30%), an increase of the peptide-specific CTL frequency was detected. In the second protocol, an increase of the peptide-specific CTL frequency was detected in all 4 patients (100%), although there were no significant beneficial clinical responses. ELISPOT assay showed peptide-specific IFN-γ responses in 2 patients in whom the peptide-specific CTL frequency in tetramer staining also was increased in both protocols. This phase I clinical study revealed that survivin-2B peptide vaccination was well tolerated. The vaccination with survivin-2B peptide mixed with IFA increased the frequency of peptide-specific CTL more effectively than vaccination with the peptide alone, although neither vaccination could induce efficient clinical responses. Considering the above, the addition of another effectual adjuvant such as a cytokine, heat shock protein, etc. to the vaccination with survivin-2B peptide mixed with IFA might induce improved immunological and clinical responses.
登录
查看更多内容
影响因子：
11.5
作者：
Idenoue, S;Hirohashi, Y;Sato, N
通讯作者：
Sato, N
影响因子：
20.3
作者：
Schmidt, SM;Schag, K;Brossart, P
通讯作者：
Brossart, P
影响因子：
82.9
作者：
Rosenberg, SA;Yang, JC;White, DE
通讯作者：
White, DE
DOI：
10.1007/s11596-007-0411-8
发表时间：
2007-08-01
影响因子：
--
作者：
Cheng Zhengjiang;Hu Lihua;Liao Xiaofeng
通讯作者：
Liao Xiaofeng
影响因子：
2.8
作者：
Hildenbrand, B.;Sauer, B.;Azemar, M.
通讯作者：
Azemar, M.