Sadanaga N, Nagashima H, Mashino K, Tahara K, Yamaguchi H, Ohta M, Fujie T, Tanaka F, Inoue H, Takesako K, Akiyoshi T, Mori M
Department of Surgery, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumihara, Beppu 874-0838, Japan.
Clin Cancer Res. 2001 Aug;7(8):2277-84.
The MAGE gene is selectively expressed in cancer tissues such as melanoma or gastrointestinal carcinomas, whereas no expression is observed in normal tissues except testis. There are several reports of successful induction of HLA class I-restricted antitumor CTLs using MAGE peptides, and some clinical trials with these immunogenic peptides were reported as effective for some patients with malignant melanoma. However, there are no similar studies in gastrointestinal carcinomas, which are important neoplasms. Autologous dendritic cells (DCs) were generated ex vivo and were pulsed with MAGE-3 peptide, depending on the patient's HLA haplotype (HLA-A2 or A24). Patients were immunized with DC pulsed with MAGE-3 peptide every 3 weeks at four times. Twelve patients with advanced gastrointestinal carcinoma (six stomach, three esophagus, and three colon) were treated, and no toxic side effects were observed. Peptide-specific CTL responses after vaccination were observed in four of eight patients. Improvement in performance status was recognized in four patients. Tumor markers decreased in seven patients. In addition, minor tumor regressions evidenced by imaging studies were seen in three patients. These results suggested that DC vaccination with MAGE-3 peptide is a safe and promising approach in the treatment of gastrointestinal carcinomas.
MAGE基因在诸如黑色素瘤或胃肠道癌等癌组织中选择性表达，而在除睾丸外的正常组织中未观察到表达。有几篇关于使用MAGE肽成功诱导HLA I类限制性抗肿瘤CTL的报道，并且一些针对这些免疫原性肽的临床试验对一些恶性黑色素瘤患者被报道是有效的。然而，在重要肿瘤胃肠道癌中没有类似的研究。根据患者的HLA单倍型（HLA - A2或A24），在体外产生自体树突状细胞（DC）并用MAGE - 3肽脉冲处理。患者每3周用MAGE - 3肽脉冲处理的DC免疫4次。治疗了12例晚期胃肠道癌患者（6例胃癌、3例食管癌和3例结肠癌），未观察到毒性副作用。8例患者中有4例在接种疫苗后观察到肽特异性CTL反应。4例患者的体能状态得到改善。7例患者的肿瘤标志物下降。此外，3例患者经影像学研究证实有轻微肿瘤消退。这些结果表明，用MAGE - 3肽进行DC疫苗接种在胃肠道癌治疗中是一种安全且有前景的方法。
