Komohara Yoshihiro, Harada Mamoru, Arima Yoshimi, Suekane Shigetaka, Noguchi Masanori, Yamada Akira, Itoh Kyogo, Matsuoka Kei
Cancer Vaccine Development Division, Kurume University Research Center for Innovative Cancer Therapy, Kurume University, Fukuoka, Japan.
J Urol. 2007 Mar;177(3):1157-62. doi: 10.1016/j.juro.2006.10.035.
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.
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.
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.
This information could facilitate the development of effective immunotherapy against renal cell carcinoma.
尽管近期针对各种恶性肿瘤的特异性免疫疗法取得了进展，但针对肾细胞癌的有效免疫疗法尚未确立。一个合理的原因是关于肾细胞癌靶抗原的信息有限。我们通过检测肾癌细胞系中的抗原表达以及测试诱导肾细胞癌反应性细胞毒性T淋巴细胞的能力，来寻找适用于肾细胞癌免疫疗法的有用癌症抗原。
使用5种肾癌细胞系检测一组癌症相关抗原的mRNA表达。此后，检测了据报道可从人白细胞抗原 - A24 +癌症患者中诱导癌症反应性细胞毒性T淋巴细胞的抗原衍生肽，以评估其从人白细胞抗原 - A24 +肾细胞癌患者外周血单个核细胞中诱导细胞毒性T淋巴细胞的潜力。
三种候选抗原，包括多药耐药相关蛋白3、多梳蛋白家族成员zeste同源物2增强子和Her2 / neu，在所有5种肾癌细胞系中均有表达。源自这些抗原的六种肽，包括多药耐药相关蛋白3（503 - 511）、多药耐药相关蛋白3（1293 - 1302）、多梳蛋白家族成员zeste同源物2增强子（291 - 299）、多梳蛋白家族成员zeste同源物2增强子（735 - 743）、Her2 / neu342 - 350和Her2 / neu485 - 493，能有效地从人白细胞抗原 - A24 +肾细胞癌患者中诱导出肽特异性且肾细胞癌反应性的细胞毒性T淋巴细胞。阻断和冷抑制试验表明，对肾细胞癌的细胞毒性取决于人白细胞抗原I类限制的肽特异性CD8 + T细胞。
这些信息有助于开发针对肾细胞癌的有效免疫疗法。
