The feasibility of Cep55/c10orf3 derived peptide vaccine therapy for colorectal carcinoma

被引:41
作者
Inoda, Satoko [1 ,2 ]
Morita, Rena [1 ,6 ]
Hirohashi, Yoshihiko [1 ]
Torigoe, Toshihiko [1 ]
Asanuma, Hiroko [3 ]
Nakazawa, Emiri [4 ]
Nakatsugawa, Munehide [1 ]
Tamura, Yasuaki [1 ]
Kamiguchi, Kenjiro [1 ]
Tsuruma, Tetsuhiro [2 ]
Terui, Takeshi [5 ]
Ishitani, Kunihiko [5 ]
Hashino, Satoshi [6 ]
Wang, Qiang [7 ,8 ]
Greene, Mark I. [7 ,8 ]
Hasegawa, Tadashi [3 ]
Hirata, Koichi [2 ]
Asaka, Masahiro [6 ]
Sato, Noriyuki [1 ]
机构
[1] Sapporo Med Univ, Sch Med, Dept Pathol, Chuo Ku, Sapporo, Hokkaido 0608556, Japan
[2] Sapporo Med Univ, Sch Med, Dept Surg, Chuo Ku, Sapporo, Hokkaido 0608556, Japan
[3] Sapporo Med Univ, Sch Med, Dept Surg Pathol, Chuo Ku, Sapporo, Hokkaido 0608556, Japan
[4] Japan Sci & Technol Agcy, Kita Ku, Sapporo, Hokkaido 0600819, Japan
[5] Higashi Sapporo Hosp, Shiroishi Ku, Sapporo, Hokkaido 0038585, Japan
[6] Hokkaido Univ, Dept Gastroenterol & Hematol, Grad Sch Med, Kita Ku, Sapporo, Hokkaido 0608638, Japan
[7] Univ Penn, Sch Med, Dept Pathol, Philadelphia, PA 19104 USA
[8] Univ Penn, Sch Med, Dept Lab Med, Philadelphia, PA 19104 USA
关键词
Cep55/c10orf3; HLA-A24; Colorectal carcinoma; CTL; Tumor antigen; PROTEIN; CENTROSOME; TUMOR; CYTOKINESIS; MIDBODY; CEP55; CELLS;
D O I
10.1016/j.yexmp.2010.10.001
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
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.
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页码:55 / 60
页数:6
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