The feasibility of Cep55/c10orf3 derived peptide vaccine therapy for colorectal carcinoma
The feasibility of Cep55/c10orf3 derived peptide vaccine therapy for colorectal carcinoma
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DOI：
10.1016/j.yexmp.2010.10.001
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发表时间：
2011-02-01
影响因子：
3.6
通讯作者：
Sato, Noriyuki
中科院分区：
文献类型：
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作者：
Inoda, Satoko;Morita, Rena;Sato, Noriyuki
在我们之前的研究中，我们证明了来自新的中心体驻留蛋白Cep55/C10orf3的多肽可以被乳腺癌患者外周血单个核细胞(PBMC)中的细胞毒性T淋巴细胞(CTL)靶向。在本报告中，我们评估了Cep55/C10orf3多肽用于结直肠癌(CRC)免疫治疗的可行性。为探讨Cep55/C10orf3在结直肠癌组织中的表达，我们用抗Cep55/C10orf3单抗进行了免疫组织化学染色。70例结直肠癌中Cep55/c10orf3弱阳性者占63%。Cep55/c10orf3的表达意向与结直肠癌的高组织学分级相一致。因此，我们假设Cep55/c10orf3也可以作为结直肠癌CTL的靶点。我们利用人类白细胞抗原(HLAA24)限制性的Cep55/C10orf3多肽，从人类白细胞抗原(HLAA24)阳性的结直肠癌患者的PBMC中产生CTL。6例结直肠癌患者中有2例Cep55/C10orf3_193(10)肽呈阳性反应，Cep55/C10orf3_193(10)肽是乳腺癌患者中唯一的免疫原肽。Cep55/c10orf3_193(10)特异性CTL克隆识别和裂解HLAA24(+)和Cep55/c10orf3(+)结直肠癌细胞系。ELISPOT法检测有1例结直肠癌患者Cep55/c10orf3_402(11)和Cep55/c10orf3_283(12)呈阳性反应，而Cep55/c10orf3_193(10)呈阴性。这些观察结果提示，人类白细胞抗原A24在结直肠癌和乳腺癌中呈现的抗原多肽库可能不同。因此，这些多肽疫苗的多肽混合物Cep55/C10orf3_193(10)。Cep55/c10orf3_402(11)和Cep55/c10orf3_283(12)可能比单一多肽更有效地治疗结直肠癌。(C)2010 Elsevier Inc.保留所有权利。
In our previous study, we demonstrated that a peptide derived from the novel centrosome residing protein Cep55/c10orf3 can be targeted by the cytotoxic T lymphocytes (CTLs) in peripheral blood mononuclear cells (PBMCs) of breast carcinoma patients. In this report, we evaluated the feasibility of cancer immunotherapy using Cep55/c10orf3 peptide for colorectal carcinoma (CRC). To evaluate the expression of Cep55/c10orf3 in CRC tissues, we performed immunohistochemical staining of using anti-Cep55/c10orf3 monoclonal antibody. Sixty-three percent cases showed weak positive for Cep55/c10orf3 in total 70 CRC cases. The Cep55/c10orf3 expression intention was collated with high histological grade of CRC. Thus, we hypothesized that Cep55/c10orf3 can also be the target of CTLs in CRC cases. We generated CTLs from PBMCs of human leukocyte antigen (HLA)-A24-positive colorectal carcinoma patients using HLA-A24-restricted Cep55/c10orf3 peptides. Two of 6 colorectal cancer patients were reactive for the Cep55/c10orf3_193(10) peptide, which was the only immunogenic peptide in breast carcinoma patients. CTL clone specific for Cep55/c10orf3_193(10) recognized and lysed HLA-A24 (+) and Cep55/c10orf3 (+) colorectal carcinoma cell lines. In addition, 1 of 6 colorectal carcinoma patients was reactive for the Cep55/c10orf3_402(11) and Cep55/c10orf3_283(12) peptides, but not for Cep55/c10orf3_193(10) with the ELISPOT assay. These observations suggest that the antigenic peptide repertoire presented by HLA-A24 in colorectal carcinoma might be different from that in breast carcinoma. Thus, these peptide vaccination peptide mixture of Cep55/c10orf3_193(10). Cep55/c10orf3_402(11) and Cep55/c10orf3_283(12) might be more effective than a single peptide in the treatment of colorectal carcinoma patients. (C) 2010 Elsevier Inc. All rights reserved.