A potent immunogenic general cancer vaccine that targets survivin, an inhibitor of apoptosis proteins
A potent immunogenic general cancer vaccine that targets survivin, an inhibitor of apoptosis proteins
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DOI：
10.1158/1078-0432.ccr-03-0817
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发表时间：
2005-02-15
影响因子：
11.5
通讯作者：
Sato, N
中科院分区：
文献类型：
--
作者：
Idenoue, S;Hirohashi, Y;Sato, N
我们先前报道了一种由CD8(+)CTL识别的人类白细胞抗原-A24限制性抗原肽Survivin-2B80-88(AYACNTSTL)。该多肽来源于Survivin蛋白，一种凋亡抑制蛋白，在多种肿瘤中表达，如腺癌、鳞状细胞癌和恶性黑色素瘤。在这份报告中，我们提供了进一步的证据，表明Survivin-2B80-88多肽可能成为多种癌症患者的有效免疫原性癌症疫苗。免疫组织化学方法检测到Survivin在大多数乳腺癌、结直肠癌和部分胃癌手术切除的原发肿瘤标本中过表达。HL A-A24/Survivin-2B80-88四聚体分析显示，RLA-A24(+)乳腺癌患者外周血单个核细胞(PBMC)中CTL前体细胞数量增加，6例乳腺癌患者PBMC经Survivin-2B80-88多肽体外刺激后，CTL前体细胞频率增加。此外，7例乳腺癌患者、6例结直肠癌患者和4例胃癌患者的PBMC均能成功地诱导出针对该多肽的CTL。这些数据表明，肿瘤组织中表达的Survivin在癌症患者中具有抗原性，不同癌症患者的PBMCs中存在Survivin-2B80-88特异性的CTL。我们的研究提出了这种多肽可能作为普通癌症疫苗适用于很大比例的人类白细胞抗原-A24(+)癌症患者的可能性。
We reported previously a HLA-A24-restricted antigenic peptide, survivin-2B80-88 (AYACNTSTL), recognized by CD8(+) CTL. This peptide was derived from survivin protein, an inhibitor of apoptosis proteins, expressed in a variety of tumors, such as adenocarcinoma, squamous cell carcinoma, and malignant melanoma. In this report; we provide further evidence that survivin-2B80-88 peptide might serve as a potent immunogenic cancer vaccine for various cancer patients. Overexpression of survivin was detected in surgically resected primary tumor specimens of most breast and colorectal cancers and some gastric cancers as assessed by immunohistochemical study. HLA-A24/survivin-2B80-88 tetramer analysis revealed that there existed an increased number of CTL precursors in peripheral blood mononuclear cells (PBMC) of RLA-A24(+) cancer patients, and in vitro stimulation of PBMCs from six breast cancer patients with survivin-2B80-88 peptide could lead to increases of the CTL precursor frequency. Furthermore, CTLs specific for this peptide were successfully induced from PBMCs in all 7 (100%) patients with breast cancers, 6 of 7 (83%) patients with colorectal cancers, and 4 of 7 (57%) patients with gastric cancers. These data indicate that survivin expressed in tumor tissues is antigenic in cancer patients, and survivin-2B80-88-specific CTLs are present in PBMCs of various cancer patients. Our study raises the possibility that this peptide may be applicable as a general cancer vaccine to a large proportion of HLA-A24(+) cancer patients.