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

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 can...

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Published in:Experimental and molecular pathology 2011-02, Vol.90 (1), p.55-60
Main Authors: Inoda, Satoko, Morita, Rena, Hirohashi, Yoshihiko, Torigoe, Toshihiko, Asanuma, Hiroko, Nakazawa, Emiri, Nakatsugawa, Munehide, Tamura, Yasuaki, Kamiguchi, Kenjiro, Tsuruma, Tetsuhiro, Terui, Takeshi, Ishitani, Kunihiko, Hashino, Satoshi, Wang, Qiang, Greene, Mark I., Hasegawa, Tadashi, Hirata, Koichi, Asaka, Masahiro, Sato, Noriyuki
Format: Article
Language:English
Subjects:
Biological and medical sciences
Cancer Vaccines - therapeutic use
Cell Cycle Proteins - immunology
Cell Cycle Proteins - metabolism
Cell Line, Tumor
Cep55/c10orf3
Colorectal carcinoma
Colorectal Neoplasms - immunology
Colorectal Neoplasms - therapy
CTL
Feasibility Studies
Female
Gastroenterology. Liver. Pancreas. Abdomen
HLA-A Antigens - immunology
HLA-A Antigens - metabolism
HLA-A24
HLA-A24 Antigen
Humans
Investigative techniques, diagnostic techniques (general aspects)
Medical sciences
Nuclear Proteins - immunology
Nuclear Proteins - metabolism
Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques
Peptides - immunology
Peptides - metabolism
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
T-Lymphocytes, Cytotoxic - immunology
T-Lymphocytes, Cytotoxic - metabolism
Tumor antigen
Tumors
Vaccines, Subunit - immunology
Vaccines, Subunit - therapeutic use
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Summary: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. ► Cep55/c10orf3 expresses in colorectal carcinoma tissues. ► The Cep55/c10orf3 expression intention was collated with high historical grade. ► Cep55/c10orf3 peptides-specific CTLs were induced from PBMCs of HLA-A24+ colorectal carcinoma patients. ► Cep55/c10orf3 peptides may be useful for colorectal carcinoma immunotherapy.
ISSN:0014-4800
1096-0945
DOI:10.1016/j.yexmp.2010.10.001