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

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 clinic...

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Bibliographic Details
Published in:Clinical cancer research 2001-08, Vol.7 (8), p.2277-2284
Main Authors: SADANAGA, Noriaki, NAGASHIMA, Hideki, AKIYOSHI, Tsuyoshi, MORI, Masaki, MASHINO, Kohjiro, TAHARA, Kouichirou, YAMAGUCHI, Hiroshi, OHTA, Mitsuhiko, FUJIE, Tatsuo, TANAKA, Fumiaki, INOUE, Hiroshi, TAKESAKO, Kazutou
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Antigens, Neoplasm - analysis
Antineoplastic agents
Biological and medical sciences
CA-19-9 Antigen - analysis
Cancer Vaccines - immunology
Carcinoembryonic Antigen - analysis
Cytotoxicity, Immunologic
Dendritic Cells - immunology
Female
Gastrointestinal Neoplasms - immunology
Gastrointestinal Neoplasms - metabolism
Gastrointestinal Neoplasms - prevention & control
Humans
Immunohistochemistry
Immunotherapy
Immunotherapy, Adoptive
Male
Medical sciences
Middle Aged
Neoplasm Proteins - immunology
Pharmacology. Drug treatments
Serpins
Treatment Outcome
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Summary: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.
ISSN:1078-0432
1557-3265