title: Adoptive immunotherapy with MUC1-mRNA transfected dendritic cells and cytotoxic lymphocytes plus gemcitabine for unresectable pancreatic cancer.
abstract: BACKGROUND
  We previously reported the clinical efficacy of adoptive immunotherapy (AIT) with dendritic cells (DCs) pulsed with mucin 1 (MUC1) peptide and cytotoxic T lymphocytes (CTLs). We also reported that gemcitabine (GEM) enhances anti-tumor immunity by suppressing regulatory T cells. Therefore, in the present study, we performed combination therapy with AIT and GEM for patients with unresectable or recurrent pancreatic cancer.
  
  
  METHODS
  Forty-two patients with unresectable or recurrent pancreatic cancer were treated. DCs were generated by culture with granulocyte macrophage colony-stimulating factor and interleukin-4 and then exposed to tumor necrosis factor-α. Mature DCs were transfected with MUC1-mRNA by electroporation (MUC1-DCs). MUC1-CTLs were induced by co-culture with YPK-1, a human pancreatic cancer cell line, and then with interleukin-2. Patients were treated with GEM, while MUC1-DCs were intradermally injected, and MUC1-CTLs were intravenously administered.
  
  
  RESULTS
  Median survival time (MST) was 13.9 months, and the 1-year survival rate was 51.1%. Of 42 patients, one patient had complete response (2.4%), three patients had partial response (7.1%) and 22 patients had stable disease (52.4%). The disease control ratio was 61.9%. The MST and 1-year survival rate of 35 patients who received more than 1 × 10(7) MUC1-DCs per injection was 16.1 months and 60.3%, respectively. Liver metastasis occurred in only 5 patients among 35 patients without liver metastasis before treatment. There were no severe toxicities associated with AIT.
  
  
  CONCLUSIONS
  AIT with MUC1-DCs and MUC1-CTLs plus GEM may be a feasible and effective treatment for pancreatic cancer.
authors.forename: Yoshitaro
authors.initials: Y
authors.lastname: Shindo
authors.forename: Shoichi
authors.initials: S
authors.lastname: Hazama
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Maeda
authors.forename: Hiroto
authors.initials: H
authors.lastname: Matsui
authors.forename: Michihisa
authors.initials: M
authors.lastname: Iida
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Suzuki
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yoshimura
authors.forename: Tomio
authors.initials: T
authors.lastname: Ueno
authors.forename: Shigefumi
authors.initials: S
authors.lastname: Yoshino
authors.forename: Kohei
authors.initials: K
authors.lastname: Sakai
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Suehiro
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yamasaki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hinoda
authors.affiliation: Department of Digestive Surgery and Surgical Oncology (Department of Surgery II), Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-kogushi, Ube, Yamaguchi 755-8505, Japan. moka@yamaguchi-u.ac.jp.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Oka
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000628:therapy*; D012333:RNA, Messenger / Q000235:genetics*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D018396:Mucin-1; D012333:RNA, Messenger; D003841:Deoxycytidine; D000093542:Gemcitabine