Identification of target antigens in specific immunotherapy for renal cell carcinoma
Identification of target antigens in specific immunotherapy for renal cell carcinoma
复制标题
DOI：
10.1016/j.juro.2006.10.035
复制
发表时间：
2007-03-01
影响因子：
6.6
通讯作者：
Matsuoka, Kei
中科院分区：
文献类型：
--
作者：
Komohara, Yoshihiro;Harada, Mamoru;Matsuoka, Kei
目的：尽管近年来针对各种恶性肿瘤的特异性免疫治疗取得了进展，但针对肾癌的有效免疫治疗尚未建立起来。一个看似合理的原因是关于肾癌靶抗原的信息有限。我们通过检测肾癌细胞株的抗原表达和诱导肾癌反应性细胞毒性T淋巴细胞的能力，寻找适用于肾癌免疫治疗的肿瘤抗原。材料和方法：以5株肾癌细胞株为材料，检测一组癌相关抗原的mRNA表达。结果：5种肾癌细胞株均表达多药耐药相关蛋白3、ZEST同源物多梳状蛋白增强子2和Her2/neu三种候选抗原。这些多药耐药相关蛋白3(503-511)、多药耐药相关蛋白3(1293-1302)、ZEST同源物多梳状蛋白增强子2(291-299)、ZEST同源物多梳状蛋白增强子2(735-743)、Her2/neu(342-350)和Her2/neu(485-493)能有效地诱导人白细胞抗原-A24(+)肾癌患者的多肽特异性和肾癌反应性细胞毒T淋巴细胞。阻断和冷抑制实验表明，肾癌的细胞毒作用依赖于人类白细胞抗原I类限制性T细胞和多肽特异性CD8(+)T细胞。结论：这些信息有助于开发有效的肾癌免疫治疗方法。
Purpose: 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.Materials and 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/neu(342-350) and Her2/neu(485-493), 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.