title: Dendritic cells transfected with heat-shock protein 70 messenger RNA for patients with hepatitis C virus-related hepatocellular carcinoma: a phase 1 dose escalation clinical trial.
abstract: BACKGROUND
  We previously reported overexpression of heat-shock protein (HSP) 70 in hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) using proteomic profiling and immunohistochemical staining (IHS). This suggested that HSP70 could be a molecular target for treatment of HCC.
  
  
  METHODS
  Twelve patients with HCV-related HCC were enrolled in a phase 1 clinical trial. Dendritic cells (DCs) transfected with HSP70 mRNA (HSP70-DCs) induced by electroporation were injected intradermally. Patients were treated three times every 3 weeks. The number of HSP70-DCs injected was 1 × 10(7) as the lowest dose, then 2 × 10(7) as the medium dose, and then 3 × 10(7) as the highest dose. Immunological analyses were performed.
  
  
  RESULTS
  No adverse effects of grade III/IV, except one grade III liver abscess at the 3 × 10(7) dose, were observed. Thus, we added three more patients to confirm whether 3 × 10(7) is an appropriate dose. Eventually, we chose 3 × 10(7) as the recommended dose of DCs. Complete response (CR) without any recurrence occurred in two patients, stable disease in five, and progression of disease in five. The two patients with CR have had no recurrence for 44 and 33 months, respectively. IHS in one patient who underwent partial hepatectomy showed infiltration of CD8+ T cells and granzyme B in tumors, indicating that the dominant immune effector cells were cytotoxic T lymphocytes with tumor-killing activity.
  
  
  CONCLUSIONS
  This study demonstrated that HSP70-DCs therapy is both safe and feasible in patients with HCV-related HCC. Further clinical trials should be considered.
authors.affiliation: Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan, y.maeda@kousei-h.jp.
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Maeda
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yoshimura
authors.forename: Hiroto
authors.initials: H
authors.lastname: Matsui
authors.forename: Yoshitaro
authors.initials: Y
authors.lastname: Shindo
authors.forename: Takao
authors.initials: T
authors.lastname: Tamesa
authors.forename: Yukio
authors.initials: Y
authors.lastname: Tokumitsu
authors.forename: Noriaki
authors.initials: N
authors.lastname: Hashimoto
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Tokuhisa
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Kouhei
authors.initials: K
authors.lastname: Sakai
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Suehiro
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hinoda
authors.forename: Koji
authors.initials: K
authors.lastname: Tamada
authors.forename: Shigefumi
authors.initials: S
authors.lastname: Yoshino
authors.forename: Shoichi
authors.initials: S
authors.lastname: Hazama
authors.forename: Masaaki
authors.initials: M
authors.lastname: Oka
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000628:therapy* / Q000821:virology*; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D005260:Female; D005500:Follow-Up Studies; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000150:complications*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007271:Injections, Intradermal; D008113:Liver Neoplasms / Q000628:therapy* / Q000821:virology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000628:therapy; D012333:RNA, Messenger / Q000235:genetics; D012074:Remission Induction; D014162:Transfection; D019076:Transgenes / Q000235:genetics; D055815:Young Adult
chemical_list: D018840:HSP70 Heat-Shock Proteins; D012333:RNA, Messenger