Proliferation potential-related protein, an ideal esophageal cancer antigen for immunotherapy, identified using complementary DNA microarray analysis.
OBJECTIVE
To establish effective antitumor immunotherapy for esophageal cancer, we tried to identify an useful target antigen of esophageal cancer.


METHODS
We did cDNA microarray analysis to find a novel candidate antigen, proliferation potential-related protein (PP-RP). We examined cytotoxicity against tumor cells in vitro and in vivo of CTLs specific to PP-RP established from esophageal cancer patients.


RESULTS
In 26 esophageal cancer tissues, an average of relative ratio of the expression of the PP-RP mRNA in cancer cells versus adjacent normal esophageal tissues was 396.2. Immunohistochemical analysis revealed that, in 20 of the 22 esophageal cancer tissues, PP-RP protein was strongly expressed only in the cancer cells and not so in normal esophageal epithelial cells. PP-RP protein contains 10 epitopes recognized by HLA-A24-restricted CTLs. These CTLs, generated from HLA-A24-positive esophageal cancer patients, had cytotoxic activity against cancer cell lines positive for both PP-RP and HLA-A24. Furthermore, adoptive transfer of the PP-RP-specific CTL line inhibited the growth of a human esophageal cancer cell line engrafted in nude mice.


CONCLUSIONS
The expression of PP-RP in esophageal cancer cells was significantly higher than in normal cells, and the CTLs recognizing PP-RP killed tumor cells in vitro and also showed tumor rejection effects in a xenograft model. Therefore, PP-RP may prove to be an ideal tumor antigen useful for diagnosis and immunotherapy for patients with esophageal cancer. cDNA microarray analysis is a useful method to identify ideal tumor-associated antigens.
Yoshitake
Yoshihiro
Y
Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Nakatsura
Tetsuya
T
Monji
Mikio
M
Senju
Satoru
S
Matsuyoshi
Hidetake
H
Tsukamoto
Hirotake
H
Hosaka
Seiji
S
Komori
Hiroyuki
H
Fukuma
Daiki
D
Ikuta
Yoshiaki
Y
Katagiri
Toyomasa
T
Furukawa
Yoichi
Y
Ito
Hiromi
H
Shinohara
Masanori
M
Nakamura
Yusuke
Y
Nishimura
Yasuharu
Y
D000328:Adult; D000368:Aged; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics* / Q000276:immunology / Q000494:pharmacology; D045744:Cell Line, Tumor; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000276:immunology / Q000494:pharmacology; D004938:Esophageal Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015234:HLA-A Antigens / Q000276:immunology; D059871:HLA-A24 Antigen; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D016219:Immunotherapy, Adoptive / Q000379:methods; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000235:genetics / Q000473:pathology; D010920:Placenta / Q000378:metabolism; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013737:Testis / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases; D023041:Xenograft Model Antitumor Assays
D000951:Antigens, Neoplasm; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; D012333:RNA, Messenger; C098584:RBBP6 protein, human; D044767:Ubiquitin-Protein Ligases