PMID- 25982372
OWN - NLM
STAT- MEDLINE
DCOM- 20151027
LR  - 20240426
IS  - 1432-0851 (Electronic)
IS  - 0340-7004 (Print)
IS  - 0340-7004 (Linking)
VI  - 64
IP  - 8
DP  - 2015 Aug
TI  - 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.
PG  - 1047-56
LID - 10.1007/s00262-015-1709-1 [doi]
AB  - 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 x 10(7) as the lowest dose, then 2 x 10(7) as the medium 
      dose, and then 3 x 10(7) as the highest dose. Immunological analyses were 
      performed. FINDINGS: No adverse effects of grade III/IV, except one grade III 
      liver abscess at the 3 x 10(7) dose, were observed. Thus, we added three more 
      patients to confirm whether 3 x 10(7) is an appropriate dose. Eventually, we 
      chose 3 x 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. INTERPRETATION: This study demonstrated that HSP70-DCs therapy is both 
      safe and feasible in patients with HCV-related HCC. Further clinical trials 
      should be considered.
FAU - Maeda, Yoshinari
AU  - Maeda Y
AD  - 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.
FAU - Yoshimura, Kiyoshi
AU  - Yoshimura K
FAU - Matsui, Hiroto
AU  - Matsui H
FAU - Shindo, Yoshitaro
AU  - Shindo Y
FAU - Tamesa, Takao
AU  - Tamesa T
FAU - Tokumitsu, Yukio
AU  - Tokumitsu Y
FAU - Hashimoto, Noriaki
AU  - Hashimoto N
FAU - Tokuhisa, Yoshihiro
AU  - Tokuhisa Y
FAU - Sakamoto, Kazuhiko
AU  - Sakamoto K
FAU - Sakai, Kouhei
AU  - Sakai K
FAU - Suehiro, Yutaka
AU  - Suehiro Y
FAU - Hinoda, Yuji
AU  - Hinoda Y
FAU - Tamada, Koji
AU  - Tamada K
FAU - Yoshino, Shigefumi
AU  - Yoshino S
FAU - Hazama, Shoichi
AU  - Hazama S
FAU - Oka, Masaaki
AU  - Oka M
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150516
PL  - Germany
TA  - Cancer Immunol Immunother
JT  - Cancer immunology, immunotherapy : CII
JID - 8605732
RN  - 0 (HSP70 Heat-Shock Proteins)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Carcinoma, Hepatocellular/*therapy/*virology
MH  - Cytotoxicity, Immunologic
MH  - Dendritic Cells/immunology/*transplantation
MH  - Female
MH  - Follow-Up Studies
MH  - HSP70 Heat-Shock Proteins/*genetics
MH  - Hepacivirus/*immunology
MH  - Hepatitis C, Chronic/*complications
MH  - Humans
MH  - Immunotherapy/*methods
MH  - Injections, Intradermal
MH  - Liver Neoplasms/*therapy/*virology
MH  - Lymphocyte Activation
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local/therapy
MH  - RNA, Messenger/genetics
MH  - Remission Induction
MH  - Transfection
MH  - Transgenes/genetics
MH  - Young Adult
PMC - PMC11028566
COIS- The authors have no conflict of interest.
EDAT- 2015/05/20 06:00
MHDA- 2015/10/28 06:00
PMCR- 2015/05/16
CRDT- 2015/05/19 06:00
PHST- 2014/10/27 00:00 [received]
PHST- 2015/05/04 00:00 [accepted]
PHST- 2015/05/19 06:00 [entrez]
PHST- 2015/05/20 06:00 [pubmed]
PHST- 2015/10/28 06:00 [medline]
PHST- 2015/05/16 00:00 [pmc-release]
AID - 1709 [pii]
AID - 10.1007/s00262-015-1709-1 [doi]
PST - ppublish
SO  - Cancer Immunol Immunother. 2015 Aug;64(8):1047-56. doi: 
      10.1007/s00262-015-1709-1. Epub 2015 May 16.