Cep55/c10orf3, a tumor antigen derived from a centrosome residing protein in breast carcinoma.

Abstract

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.

• Authors: Satoko Inoda, Yoshihiko Hirohashi, Toshihiko Torigoe, Munehide Nakatsugawa, Kenji Kiriyama, Emiri Nakazawa, Kenji Harada, Hideo Takasu, Yasuaki Tamura, Kenjiro Kamiguchi, Hiroko Asanuma, Tetsuhiro Tsuruma, Takeshi Terui, Kunihiko Ishitani, Tosei Ohmura, Qiang Wang, Mark I Greene, Tadashi Hasegawa, Koichi Hirata, Noriyuki Sato
• Journal: Journal of immunotherapy (Hagerstown, Md. : 1997) (J Immunother) Vol. 32 Issue 5 Pg. 474-85 (Jun 2009) ISSN: 1537-4513 [Electronic] United States
• PMID: 19609239 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Cell Cycle Proteins
• Cep55 protein, human
• HLA-A Antigens
• HLA-A*24:02 antigen
• HLA-A24 Antigen
• Nuclear Proteins
• Peptide Fragments

Topics

• Antigens, Neoplasm (immunology)
• Breast Neoplasms (immunology, pathology, therapy)
• Cell Cycle Proteins (immunology, metabolism)
• Centrosome (metabolism)
• Cloning, Molecular
• Drug Resistance, Neoplasm
• Female
• Gene Expression Profiling
• HCT116 Cells
• HLA-A Antigens (metabolism)
• HLA-A24 Antigen
• Humans
• Immunohistochemistry
• Immunotherapy, Active
• K562 Cells
• Microarray Analysis
• Nuclear Proteins (immunology, metabolism)
• Peptide Fragments (chemistry, genetics, immunology, metabolism)
• Protein Binding
• Protein Interaction Domains and Motifs (immunology)
• Protein Transport
• T-Lymphocytes, Cytotoxic (immunology, metabolism, pathology)