Cep55/c10orf3, a Tumor Antigen Derived From a Centrosome Residing Protein in Breast Carcinoma
Cep55/c10orf3, a Tumor Antigen Derived From a Centrosome Residing Protein in Breast Carcinoma
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DOI：
10.1097/cji.0b013e3181a1d109
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发表时间：
2009-06-01
影响因子：
3.9
通讯作者：
Sato, Noriyuki
中科院分区：
文献类型：
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作者：
Inoda, Satoko;Hirohashi, Yoshihiko;Sato, Noriyuki
肿瘤相关抗原的鉴定可能有助于治疗恶性疾病患者的疫苗接种策略。我们发现中心体蛋白 Cep55/c10orf3 作为一种新型乳腺癌相关肿瘤相关抗原。在多种肿瘤细胞系中均可检测到 Cep55/c10orf3 mRNA。除睾丸和胸腺外，在正常组织中几乎检测不到表达。此外，单克隆抗 Cep55/c10orf3 抗体 (#11-55) 可在 69.8% 的乳腺癌、25% 的结直肠癌和 57.8% 的肺癌组织中检测到 Cep55/c10orf3 蛋白。 Cep55/c10orf3蛋白的表达与雌激素受体、孕激素受体等激素受体或p185(HER2/neu)的表达模式没有任何关系。我们设计了 11 种展示人类白细胞抗原 A24 结合基序的肽。一种 Cep55/c10orf3 肽 Cep55/c10orf3_193(10) (VYVKGLLAKI) 在 3 名 Cep55/c10orf3 (#11-55) 阳性乳腺癌患者中的 3 名中诱导细胞毒性 T 淋巴细胞 (CTL)。 Cep55/c10orf3_193(10) 特异性 CTL 克隆还可以识别人类白细胞抗原 A24 (+) 癌细胞系上展示的 Cep55/c10orf3 (+)。这些数据表明Cep55/c10orf3肽是由乳腺癌细胞自然呈递的，并且可以在体内引起CTL克隆扩增。单克隆抗体 #11-55 和 Cep55/c10orf3_193(10) 肽可用作激素治疗或抗 p185(HER2/neu) 单克隆抗体治疗耐药的乳腺癌患者治疗策略的一部分。
Identification of tumor-associated antigens may facilitate vaccination strategies to treat patients with malignant diseases. We have found that the centrosomal protein, Cep55/c10orf3 acts as a novel breast carcinoma-associated tumor-associated antigen. Cep55/c10orf3 mRNA was detectable in a wide variety of tumor cell lines. Expression was barely detectable in normal tissues except for testis and thymus. Moreover, Cep55/c10orf3 protein could be detected by a monoclonal anti-Cep55/c10orf3 antibody (#11-55) in 69.8% of breast carcinoma, 25% of colorectal carcinoma, and 57.8% Of lung carcinoma tissues. The expression of Cep55/c10orf3 protein did not show any relationship with the hormone receptors such as estrogen receptor and progesterone receptor or expression patterns of p185(HER2/neu). We designed 11 peptides which displayed a human leukocyte antigen-A24 binding motif. One Cep55/c10orf3-peptide, Cep55/c10orf3_193(10) (VYVKGLLAKI), induced cytotoxic T lymphocytes (CTLs) in 3 of 3 patients with Cep55/c10orf3 (#11-55)positive breast carcinoma. A Cep55/c10orf3_193(10)-specific CTL clone could also recognize Cep55/c10orf3 (+) displayed on human leukocyte antigen-A24 (+) cancer cell lines. These data indicate that Cep55/c10orf3 peptides were naturally presented by breast cancer cells and can cause CTL clonal expansion in vivo. Monoclonal antibody #11-55 and the Cep55/c10orf3_193(10) peptides may be useful as part of a therapeutic strategy for hormonal therapy or anti-p185(HER2/neu) monoclonal antibody therapy-resistant breast carcinoma patients.