Tanaka Fumiaki, Haraguchi Naotsugu, Isikawa Kenji, Inoue Hiroshi, Mori Masaki
Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan.
Oncol Rep. 2008 Nov;20(5):1111-6.
Dendritic cells (DCs) loaded with tumor antigens have been emerging as a new strategy in cancer treatment. The MAGE genes are selectively expressed in a variety of cancer tissues such as melanoma or gastrointestinal carcinomas. However, no expression is observed in normal tissues except testis. There are several reports on clinical trials with these immunogenic peptides including MAGE gene-derived, which were shown to be effective for some patients with carcinomas. We previously reported a clinical trial treating gastrointestinal carcinoma patients with immature DC and MAGE peptides via intravenous injection. Autologous DCs were generated ex vivo and were pulsed with MAGE-3 peptide, depending on the patient's HLA haplotype (HLA-A02 or A24). In this study, patients were immunized with mature DCs pulsed with the MAGE-3 peptide four times every 2 weeks via s.c. injection close to the axilla and inguinal lymph nodes. Twenty-eight patients with advanced gastrointestinal carcinoma were treated and no toxic side effects were observed. Peptide-specific CTL responses, improvement in performance status, tumor marker decrease and minor tumor regressions after vaccination were observed in some patients. These results suggested that DC vaccination with the MAGE-3 peptide would be safe and can exhibit antitumor effects even in the patients with advanced gastrointestinal carcinoma who were previously treated with chemotherapy or radiation therapy.
负载肿瘤抗原的树突状细胞(DCs)已成为癌症治疗的一种新策略。MAGE基因在多种癌症组织中选择性表达,如黑色素瘤或胃肠道癌。然而,除睾丸外,在正常组织中未观察到表达。有几篇关于这些免疫原性肽的临床试验报告,包括MAGE基因衍生的肽,这些肽对一些癌症患者显示出有效性。我们之前报道了一项通过静脉注射用未成熟DC和MAGE肽治疗胃肠道癌患者的临床试验。根据患者的HLA单倍型(HLA - A02或A24),在体外产生自体DC,并与MAGE - 3肽脉冲结合。在本研究中,患者通过在靠近腋窝和腹股沟淋巴结处皮下注射,每2周用MAGE - 3肽脉冲处理的成熟DC免疫4次。28例晚期胃肠道癌患者接受了治疗,未观察到毒性副作用。在一些患者中观察到了肽特异性CTL反应、体能状态改善、肿瘤标志物下降以及接种疫苗后轻微的肿瘤消退。这些结果表明,用MAGE - 3肽进行DC疫苗接种是安全的,甚至在先前接受过化疗或放疗的晚期胃肠道癌患者中也能表现出抗肿瘤作用。