Identification of target antigens in specific immunotherapy for renal cell carcinoma.
OBJECTIVE
Effective immunotherapy against renal cell carcinoma has not yet been established despite recent advances in specific immunotherapy for various malignancies. A plausible reason is limited information about target antigens of renal cell carcinoma. We searched for useful cancer antigens applicable to immunotherapy for renal cell carcinoma by examining antigen expression in renal cell carcinoma cell lines and testing the ability to induce renal cell carcinoma reactive cytotoxic T lymphocytes.


METHODS
mRNA expression of a panel of cancer associated antigens was examined using 5 renal cell carcinoma cell lines. Thereafter antigen derived peptides reported to induce cancer reactive cytotoxic T lymphocytes from human leukocyte antigen-A24+ patients with cancer were examined for their potential to induce cytotoxic T lymphocytes from peripheral blood mononuclear cells of human leukocyte antigen-A24+ patients with renal cell carcinoma.


RESULTS
Three candidate antigens, including multidrug resistance-associated protein 3, polycomb group protein enhancer of zeste homologue 2 and Her2/neu, were expressed in all 5 renal cell carcinoma cell lines. Six peptides derived from these antigens, including multidrug resistance-associated protein 3(503-511), multidrug resistance-associated protein 3(1293-1302), polycomb group protein enhancer of zeste homologue 2(291-299), polycomb group protein enhancer of zeste homologue 2(735-743), Her2/neu342-350 and Her2/neu485-493, efficiently induced peptide specific and renal cell carcinoma reactive cytotoxic T lymphocytes from human leukocyte antigen-A24+ patients with renal cell carcinoma. Blocking and cold inhibition assays revealed that cytotoxicity against renal cell carcinoma depended on human leukocyte antigen class I restricted and peptide specific CD8+ T cells.


CONCLUSIONS
This information could facilitate the development of effective immunotherapy against renal cell carcinoma.
Komohara
Yoshihiro
Y
Cancer Vaccine Development Division, Kurume University Research Center for Innovative Cancer Therapy, Kurume University, Fukuoka, Japan.
Harada
Mamoru
M
Arima
Yoshimi
Y
Suekane
Shigetaka
S
Noguchi
Masanori
M
Yamada
Akira
A
Itoh
Kyogo
K
Matsuoka
Kei
K
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000276:immunology; D018528:ATP-Binding Cassette Transporters / Q000276:immunology; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000628:therapy; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000276:immunology; D000071221:Enhancer of Zeste Homolog 2 Protein; D006801:Humans; D007167:Immunotherapy; D007680:Kidney Neoplasms / Q000276:immunology* / Q000628:therapy; D063151:Polycomb Repressive Complex 2; D012333:RNA, Messenger / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*; D014157:Transcription Factors / Q000276:immunology
D018435:ATP Binding Cassette Transporter, Subfamily B; D018528:ATP-Binding Cassette Transporters; D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D014157:Transcription Factors; C095122:multidrug resistance protein 3; C498409:EZH2 protein, human