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 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.
Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, chuo-ku, Sapporo 060-8556, Japan.
Satoko
S
Inoda
Rena
R
Morita
Yoshihiko
Y
Hirohashi
Toshihiko
T
Torigoe
Hiroko
H
Asanuma
Emiri
E
Nakazawa
Munehide
M
Nakatsugawa
Yasuaki
Y
Tamura
Kenjiro
K
Kamiguchi
Tetsuhiro
T
Tsuruma
Takeshi
T
Terui
Kunihiko
K
Ishitani
Satoshi
S
Hashino
Qiang
Q
Wang
Mark I
MI
Greene
Tadashi
T
Hasegawa
Koichi
K
Hirata
Masahiro
M
Asaka
Noriyuki
N
Sato
D019496:Cancer Vaccines / Q000627:therapeutic use*; D018797:Cell Cycle Proteins / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000276:immunology / Q000628:therapy*; D005240:Feasibility Studies; D005260:Female; D015234:HLA-A Antigens / Q000276:immunology / Q000378:metabolism; D059871:HLA-A24 Antigen; D006801:Humans; D009687:Nuclear Proteins / Q000276:immunology* / Q000378:metabolism; D010455:Peptides / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D022223:Vaccines, Subunit / Q000276:immunology / Q000627:therapeutic use*
D019496:Cancer Vaccines; D018797:Cell Cycle Proteins; C505378:Cep55 protein, human; D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; D009687:Nuclear Proteins; D010455:Peptides; D022223:Vaccines, Subunit