Inoda Satoko, Hirohashi Yoshihiko, Torigoe Toshihiko, Nakatsugawa Munehide, Kiriyama Kenji, Nakazawa Emiri, Harada Kenji, Takasu Hideo, Tamura Yasuaki, Kamiguchi Kenjiro, Asanuma Hiroko, Tsuruma Tetsuhiro, Terui Takeshi, Ishitani Kunihiko, Ohmura Tosei, Wang Qiang, Greene Mark I, Hasegawa Tadashi, Hirata Koichi, Sato Noriyuki
Department of Pathology, Sapporo Medical University, School of Medicine, Chuo-Ku, Sapporo, Japan.
J Immunother. 2009 Jun;32(5):474-85. doi: 10.1097/CJI.0b013e3181a1d109.
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.
肿瘤相关抗原的鉴定可能有助于制定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是一种新型的乳腺癌相关肿瘤抗原。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其表达。此外，在69.8%的乳腺癌、25%的结直肠癌和57.8%的肺癌组织中，可通过单克隆抗Cep55/c10orf3抗体（#11-55）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的表达模式均无关联。我们设计了11种具有人白细胞抗原-A24结合基序的肽。一种Cep55/c10orf3肽，即Cep55/c10orf3_193(10)（VYVKGLLAKI），在3例Cep55/c10orf3（#11-55）阳性乳腺癌患者中诱导出了细胞毒性T淋巴细胞（CTL）。一个Cep55/c10orf3_193(10)特异性CTL克隆也能够识别在人白细胞抗原-A24（+）癌细胞系上展示的Cep55/c10orf3（+）。这些数据表明，Cep55/c10orf3肽由乳腺癌细胞自然呈递，并且能够在体内引起CTL克隆扩增。单克隆抗体#11-55和Cep55/c10orf3_193(10)肽可能作为激素治疗或抗p185 HER2/neu单克隆抗体治疗耐药乳腺癌患者治疗策略的一部分而发挥作用。
