Immunogenic enhancement and clinical effect by type-I interferon of anti-apoptotic protein, survivin-derived peptide vaccine, in advanced colorectal cancer patients
Immunogenic enhancement and clinical effect by type-I interferon of anti-apoptotic protein, survivin-derived peptide vaccine, in advanced colorectal cancer patients
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DOI：
10.1111/j.1349-7006.2011.01918.x
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发表时间：
2011-06-01
期刊：
影响因子：
5.7
通讯作者：
Hirata, Koichi
中科院分区：
文献类型：
--
作者：
Kameshima, Hidekazu;Tsuruma, Tetsuhiro;Hirata, Koichi
我们以前发现了一种人类白细胞抗原(HLA)-A24限制性抗原肽，Survivin-2B80-88，可被CD8+细胞毒性T淋巴细胞(CTL)识别。随后，我们尝试将这种表位多肽单独用于某些恶性肿瘤的临床试验，结果产生了临床和免疫学反应，尽管它们作为癌症疫苗的潜力不足以作为常规临床使用。在目前的研究中，为了评估Survivin-2B80-88肽的免疫原性是否可以通过其他疫苗接种方案来增强，我们在晚期结肠癌患者中进行了两种接种方案的临床试验：(I)Survivin-2B80-88+不完全弗氏佐剂(IFA)；(Ii)Survivin-2B80-88+IFA和I型干扰素(干扰素)-α。我们的研究表明，尽管Survivin-2B80-88联合IFA与单独应用Survivin-2B80-88的疗效无明显差异，但联合应用Survivin-2B80-88联合IFA和干扰素α可改善患者的临床症状，增强患者的免疫应答。对Survivin-2B80-88多肽特异性CTL的四聚体分析表明，在8名患者中，有4名患者接种该方案后，这种CTL至少增加了一倍。在这些患者中，酶联免疫吸附斑点(ELISPOT)结果也得到了增强。随后通过多肽特异性CTL的细胞分选分离单细胞克隆的研究表明，每个CTL克隆确实不仅是多肽特异性的，而且在表达HLA-A24和Survivin分子的背景下对人类癌细胞具有细胞毒作用。综上所述，这些结果表明，结肠癌患者接种Survivin-2B80-88联合IFA和干扰素α可以被认为是一种非常有效的免疫治疗方案，该方案可能适用于其他癌症。(《癌症科学》2011；102：1181-1187)。
We previously identified a human leukocyte antigen (HLA)-A24-restricted antigenic peptide, survivin-2B80-88, recognized by CD8+ cytotoxic T lymphocytes (CTL). Subsequently, we attempted clinical trials with this epitope peptide alone for some malignancies, resulting in clinical and immunological responses, although their potential was not strong enough for routine clinical use as a cancer vaccine. In the current study, to assess whether immunogenicity of the survivin-2B80-88 peptide could be enhanced with other vaccination protocols, we performed clinical trials in advanced colon cancer patients with two vaccination protocols: (i) survivin-2B80-88 plus incomplete Freund's adjuvant (IFA); and (ii) survivin-2B80-88 plus IFA and a type-I interferon (IFN), IFN alpha. Our data clearly indicated that, although the effect of survivin-2B80-88 plus IFA was not significantly different from that with survivin-2B80-88 alone, treatment with the vaccination protocol of survivin-2B80-88 plus IFA and IFN alpha resulted in clinical improvement and enhanced immunological responses of patients. Tetramer analysis of survivin-2B80-88 peptide-specific CTL demonstrated that such CTL were increased at least twofold after vaccination with this protocol in four of eight patients. In these patients, enzyme-linked immunosorbent spot (ELISPOT) results were also enhanced. Subsequent study of single-cell clone separation by cell sorting of peptide-specific CTL showed that each CTL clone was indeed not only peptide-specific but also cytotoxic against human cancer cells in the context of the expression of both HLA-A24 and survivin molecules. Taken together, these results indicate that vaccination of colon cancer patients with survivin-2B80-88 plus IFA and IFN alpha can be considered to be a very potent immunotherapeutic regimen, and that this protocol might work for other cancers. (Cancer Sci 2011; 102: 1181-1187).