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Clinical Cancer Research Vol. 7, 2277-2284, August 2001
© 2001 American Association for Cancer Research

Regular Articles

Dendritic Cell Vaccination with MAGE Peptide Is A Novel Therapeutic Approach for Gastrointestinal Carcinomas1

Noriaki Sadanaga, Hideki Nagashima, Kohjiro Mashino, Kouichirou Tahara, Hiroshi Yamaguchi, Mitsuhiko Ohta, Tatsuo Fujie, Fumiaki Tanaka, Hiroshi Inoue, Kazutou Takesako, Tsuyoshi Akiyoshi and Masaki Mori2

Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu 874-0838 [N. S., H. N., K. M., K. Tah., H. Y., M. O., T. F., F. T., H. I., M. M.]; Biotechnology Research Laboratories, Takara Shuzo Company, Limited, Otsu, Shiga 520-2134 [K. Tak.]; and Kyushu Central Hospital, Fukuoka 811-8588 [T. A.], Japan

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.




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Copyright © 2001 by the American Association for Cancer Research.