TY - JOUR
T1 - Dendritic cells transfected with heat-shock protein 70 messenger RNA for patients with hepatitis C virus-related hepatocellular carcinoma
T2 - A phase 1 dose escalation clinical trial
AU - Maeda, Yoshinari
AU - Yoshimura, Kiyoshi
AU - Matsui, Hiroto
AU - Shindo, Yoshitaro
AU - Tamesa, Takao
AU - Tokumitsu, Yukio
AU - Hashimoto, Noriaki
AU - Tokuhisa, Yoshihiro
AU - Sakamoto, Kazuhiko
AU - Sakai, Kouhei
AU - Suehiro, Yutaka
AU - Hinoda, Yuji
AU - Tamada, Koji
AU - Yoshino, Shigefumi
AU - Hazama, Shoichi
AU - Oka, Masaaki
PY - 2015/5/16
Y1 - 2015/5/16
N2 - 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 3Âweeks. The number of HSP70-DCs injected was 1Â×Â107 as the lowest dose, then 2Â×Â107 as the medium dose, and then 3Â×Â107 as the highest dose. Immunological analyses were performed. Findings: No adverse effects of grade III/IV, except one grade III liver abscess at the 3Â×Â107 dose, were observed. Thus, we added three more patients to confirm whether 3Â×Â107 is an appropriate dose. Eventually, we chose 3Â×Â107 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 33Âmonths, 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.
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 3Âweeks. The number of HSP70-DCs injected was 1Â×Â107 as the lowest dose, then 2Â×Â107 as the medium dose, and then 3Â×Â107 as the highest dose. Immunological analyses were performed. Findings: No adverse effects of grade III/IV, except one grade III liver abscess at the 3Â×Â107 dose, were observed. Thus, we added three more patients to confirm whether 3Â×Â107 is an appropriate dose. Eventually, we chose 3Â×Â107 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 33Âmonths, 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.
KW - Dendritic cell
KW - Electroporation
KW - Heat-shock protein 70
KW - Hepatocellular carcinoma
KW - Immunotherapy
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U2 - 10.1007/s00262-015-1709-1
DO - 10.1007/s00262-015-1709-1
M3 - Article
C2 - 25982372
AN - SCOPUS:84937969182
SN - 0340-7004
VL - 64
SP - 1047
EP - 1056
JO - Cancer Immunology Immunotherapy
JF - Cancer Immunology Immunotherapy
IS - 8
ER -