Nishiyama T, Tachibana M, Horiguchi Y, Nakamura K, Ikeda Y, Takesako K, Murai M
Department of Urology, Radiology School of Medicine, Keio University, Tokyo, Japan.
Clin Cancer Res. 2001 Jan;7(1):23-31.
Recent investigations have demonstrated the efficacy of autologous dendritic cells (DCs) pulsed with tumor antigens to generate tumor-specific CTLs against cancer cells. Melanoma antigens (MAGE) are a family of tumor-specific antigens shown to be expressed in various tumors, including bladder cancers and melanoma, but not in normal tissues except for the testis. Because invasive bladder cancers are frequently reported to express MAGE, we explored the possibility of establishing a new immunotherapeutic modality against advanced bladder cancer using autologous DCs pulsed with one of the MAGE-3 epitope peptides (IMPKAGLLI), which is synthesized to bind specifically to HLA-A24. A MAGE-3-expressing bladder cancer cell line, FY, was newly established from a lymph node metastasis of bladder cancer in a HLA-A24+ patient. The FY cell-specific CTL response was significantly higher when CTL was induced by autologous DCs pulsed with IMPKAGLLI than by FY cells alone or by nonpulsed DCs in vitro. A total of four HLA-A24+ patients with advanced MAGE-3+ bladder cancers were treated with s.c. injections of autologous DCs pulsed with IMPKAGLLI every 2 weeks for a minimum of 6 and a maximum of 18 times. Three of four patients showed significant reductions in the size of lymph node metastases and/or liver metastasis. No significant untoward side effects were noted in these patients. This study indicated that, at sometime in the future, tumor-specific DC-based cancer immunotherapy may be useful as an additional treatment modality against advanced bladder cancer.
近期研究已证实，用肿瘤抗原脉冲处理的自体树突状细胞（DCs）可产生针对癌细胞的肿瘤特异性细胞毒性T淋巴细胞（CTLs），具有显著疗效。黑色素瘤抗原（MAGE）是一类肿瘤特异性抗原，已证实在包括膀胱癌和黑色素瘤在内的多种肿瘤中表达，但除睾丸外，在正常组织中不表达。由于侵袭性膀胱癌常被报道表达MAGE，我们探索了使用与MAGE-3表位肽之一（IMPKAGLLI）脉冲处理的自体DCs建立一种针对晚期膀胱癌的新型免疫治疗方法的可能性，该表位肽经合成后可特异性结合HLA-A24。从一名HLA-A24+患者的膀胱癌淋巴结转移灶中新建立了一株表达MAGE-3的膀胱癌细胞系FY。在体外，当用IMPKAGLLI脉冲处理的自体DCs诱导CTL时，FY细胞特异性CTL反应显著高于单独使用FY细胞或未脉冲处理的DCs诱导的CTL反应。共有4例HLA-A24+的晚期MAGE-3+膀胱癌患者接受治疗，每2周皮下注射一次用IMPKAGLLI脉冲处理的自体DCs，最少6次，最多18次。4例患者中有3例的淋巴结转移灶和/或肝转移灶大小显著缩小。这些患者未出现明显的不良副作用。本研究表明，在未来的某个时候，基于肿瘤特异性DCs的癌症免疫治疗可能作为一种针对晚期膀胱癌的辅助治疗方法发挥作用。
