title: A combination therapy of gemcitabine with immunotherapy for patients with inoperable locally advanced pancreatic cancer.
abstract: OBJECTIVE
  Dendritic cell (DC) therapy frequently induces a measurable immune response. However clinical responses are seen in a minority of patients, presumably due to insufficient expansion of antigen-specific cytotoxic T lymphocytes (CTLs) capable of eradicating tumor cells. To increase therapeutic efficacy of DC-based vaccination, we have undertaken the first clinical trial involving a combination therapy of gemcitabine (GEM) with immunotherapy for patients with inoperable locally advanced pancreatic cancer.
  
  
  METHODS
  Patients (n = 5) received the treatment course, which consisted of intravenous GEM administration at 1000 mg/m (day 1) and the endoscopic ultrasound-guided fine-needle injection of OK432-pulsed DCs into a tumor, followed by intravenous infusion of lymphokine-activated killer cells stimulated with anti-CD3 monoclonal antibody (CD3-LAKs) (day 4), at 2-week intervals.
  
  
  RESULTS
  No serious treatment-related adverse events were observed during the study period. Three of the 5 patients demonstrated effective responses to this clinical trial; 1 had partial remission and 2 had long stable disease more than 6 months. In the patient with partial remission, it has been shown that DC-based vaccination combined with GEM administration induces tumor antigen-specific CTLs.
  
  
  CONCLUSIONS
  This combined therapy was considered to be synergistically effective and may have a role in the therapy of pancreatic cancer for inducing tumor antigen-specific CTLs.
authors.affiliation: Department of Endoscopy, Nagoya University, Nagoya City, Japan. hirooka@med.nagoya-u.ac.jp
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Hirooka
authors.forename: Akihiro
authors.initials: A
authors.lastname: Itoh
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kawashima
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hara
authors.forename: Koji
authors.initials: K
authors.lastname: Nonogaki
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Kasugai
authors.forename: Eizaburo
authors.initials: E
authors.lastname: Ohno
authors.forename: Takuya
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsubara
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Ishigami
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Katano
authors.forename: Naoki
authors.initials: N
authors.lastname: Ohmiya
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Niwa
authors.forename: Koji
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Toru
authors.initials: T
authors.lastname: Kaneko
authors.forename: Mie
authors.initials: M
authors.lastname: Nieda
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yokokawa
authors.forename: Hidemi
authors.initials: H
authors.lastname: Goto
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000494:pharmacology*; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000009:adverse effects / Q000379:methods; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology / Q000637:transplantation*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000276:immunology*; D010865:Pilot Projects; D012720:Severity of Illness Index; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine