title: Induction of peptide-specific immune response in patients with primary malignant melanoma of the esophagus after immunotherapy using dendritic cells pulsed with MAGE peptides.
abstract: Primary malignant melanoma of the esophagus (PMME) is a very rare disease with an extremely poor prognosis. Surgery is currently considered its best treatment, while any other measures are ineffective. We studied the effect of active specific immunotherapy using monocyte-derived dendritic cells (DCs) pulsed with the epitope peptides of melanoma-associated antigens (MAGE-1, MAGE-3) in patients with PMME after surgery, for the first time. The patient received passive immunotherapy with lymphokine-activated killer cells concomitantly. Two HLA-A24-positive patients with PMME were treated. Both patients initially received radical esophagectomy with regional lymphadenectomy, followed by adjuvant chemotherapy with dacarbazine, nimustine, vincristine and interferon-alpha. In the case 1 patient, active specific immunotherapy was used to treat a large abdominal lymph node metastasis that became obvious 21 months after surgery. The disease remained stable for 5 months, and the patient survived for 12 months after the initiation of immunotherapy. In the case 2 patient, immunotherapy was tried as post-operative adjuvant treatment after adjuvant chemotherapy. There was no tumor recurrence for 16 months after the immunotherapy. As of 49 months after esophagectomy, the patient is still alive. In both patients, the ability of peripheral lymphocytes to produce IFN-gamma in vitro in response to peptide stimulation was significantly enhanced and delayed-type hypersensitivity skin test response to MAGE-3 peptide was turned positive after immunotherapy. In conclusion, active specific immunotherapy for PMME with the use of DCs and MAGE peptides was safe and capable of inducing peptide-specific immune responses. This case report warrants further clinical evaluation of this immunotherapy for PMME.
authors.affiliation: Department of Surgery and Oncology of Digestive System, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. yueda@koto.kpu-m.ac.jp
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ueda
authors.forename: Keiji
authors.initials: K
authors.lastname: Shimizu
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Itoh
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Fuji
authors.forename: Kei
authors.initials: K
authors.lastname: Naito
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shiozaki
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shimizu
authors.forename: Arihiro
authors.initials: A
authors.lastname: Iwamoto
authors.forename: Hidemasa
authors.initials: H
authors.lastname: Tamai
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Yamagishi
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology*; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000276:immunology*; D000939:Epitopes; D004938:Esophageal Neoplasms / Q000276:immunology* / Q000628:therapy*; D016629:Esophagectomy; D006801:Humans; D016219:Immunotherapy, Adoptive; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000628:therapy*; D058950:Melanoma-Specific Antigens; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D000939:Epitopes; C072011:MAGEA1 protein, human; C072013:MAGEA3 protein, human; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins