title: Combined therapy of transcatheter hepatic arterial embolization with intratumoral dendritic cell infusion for hepatocellular carcinoma: clinical safety.
abstract: The curative treatments for hepatocellular carcinoma (HCC), including surgical resection and radiofrequency ablation (RFA), do not prevent tumour recurrence effectively. Dendritic cell (DC)-based immunotherapies are believed to contribute to the eradication of the residual and recurrent tumour cells. The current study was designed to assess the safety and bioactivity of DC infusion into tumour tissues following transcatheter hepatic arterial embolization (TAE) for patients with cirrhosis and HCC. Peripheral blood mononuclear cells (PBMCs) were differentiated into phenotypically confirmed DCs. Ten patients were administered autologous DCs through an arterial catheter during TAE treatment. Shortly thereafter, some HCC nodules were treated additionally to achieve the curative local therapeutic effects. There was no clinical or serological evidence of adverse events, including hepatic failure or autoimmune responses in any patients, in addition to those due to TAE. Following the infusion of (111)Indium-labelled DCs, DCs were detectable inside and around the HCC nodules for up to 17 days, and were associated with lymphocyte and monocyte infiltration. Interestingly, T lymphocyte responses were induced against peptides derived from the tumour antigens, Her-2/neu, MRP3, hTERT and AFP, 4 weeks after the infusion in some patients. The cumulative survival rates were not significantly changed by this strategy. These results demonstrate that transcatheter arterial DC infusion into tumour tissues following TAE treatment is feasible and safe for patients with cirrhosis and HCC. Furthermore, the antigen-non-specific, immature DC infusion may induce immune responses to unprimed tumour antigens, providing a plausible strategy to enhance tumour immunity.
authors.affiliation: Disease Control and Homeostasis, Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamoto
authors.forename: E
authors.initials: E
authors.lastname: Mizukoshi
authors.forename: H
authors.initials: H
authors.lastname: Tsuji
authors.forename: Y
authors.initials: Y
authors.lastname: Sakai
authors.forename: M
authors.initials: M
authors.lastname: Kitahara
authors.forename: K
authors.initials: K
authors.lastname: Arai
authors.forename: T
authors.initials: T
authors.lastname: Yamashita
authors.forename: K
authors.initials: K
authors.lastname: Yokoyama
authors.forename: N
authors.initials: N
authors.lastname: Mukaida
authors.forename: K
authors.initials: K
authors.lastname: Matsushima
authors.forename: O
authors.initials: O
authors.lastname: Matsui
authors.forename: S
authors.initials: S
authors.lastname: Kaneko
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000276:immunology / Q000628:therapy*; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D018572:Disease-Free Survival; D004621:Embolization, Therapeutic / Q000379:methods*; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods; D008103:Liver Cirrhosis / Q000150:complications; D008113:Liver Neoplasms / Q000209:etiology / Q000276:immunology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome