Original Article
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Dec 28, 2011; 17(48): 5260-5266
Published online Dec 28, 2011. doi: 10.3748/wjg.v17.i48.5260
Hepatocellular carcinoma-specific immunotherapy with synthesized α1,3- galactosyl epitope-pulsed dendritic cells and cytokine-induced killer cells
Ying Qiu, Ming-Bao Xu, Mark M Yun, Yi-Zhong Wang, Rui-Ming Zhang, Xing-Kai Meng, Xiao-Hui Ou-Yang, Sheng Yun
Ying Qiu, Rui-Ming Zhang, Xing-Kai Meng, Xiao-Hui Ou-Yang, Sheng Yun, The First Teaching Hospital, Inner Mongolia Medical College, Huhhot 010050, Inner Mongolia Autonomous Region, China
Ming-Bao Xu, The Armed Police General Hospital, Beijing 100036, China
Mark M Yun, Medical School of UCL, London WC1E 6BT, United Kingdom
Yi-Zhong Wang, Sheng Yun, Aerospace Medical College, Peking University, Beijing 100049, China
Ying Qiu, Department of Clinical Sciences, King’s College Hospital, London SE5 9NU, United Kingdom
Sheng Yun, Clinical Sciences Centre, MRC, Hammersmith Hospital Campus, London W12 0NN, United Kingdom
Author contributions: Qiu Y and Xu MB contributed equally to this paper, they performed the majority of the work; Yun MM analyzed the data; Wang YZ contributed to the flow cytometric analysis of blood samples; Zhang RM, Meng XK and Ou-Yang XH coordinated and collected the tumor samples; Yun S proposed the study and wrote the first draft.
Supported by Hong Kong Wang Kuan Cheng Grant; and Inner Mongolia Stem Cell Grant, No. kjk10jhg
Correspondence to: Sheng Yun, Professor, Department of Oncology, The First Teaching Hospital, Inner Mongolia Medical College, No. 1, Tongdao BeiJie, Huhhot 010050, Inner Mongolia Autonomous Region, China. sheng.yun@hotmail.co.uk
Telephone: +86-471-6637582  Fax: +86-471-6965931
Received: May 5, 2011
Revised: July 14, 2011
Accepted: July 21, 2011
Published online: December 28, 2011
Abstract

AIM: To evaluate the safety and clinical efficacy of a new immunotherapy using both α-Gal epitope-pulsed dendritic cells (DCs) and cytokine-induced killer cells.

METHODS: Freshly collected hepatocellular carcinoma (HCC) tumor tissues were incubated with a mixture of neuraminidase and recombinant α1,3-galactosyltransferase (α1,3GT) to synthesize α-Gal epitopes on carbohydrate chains of the glycoproteins of tumor membranes. The subsequent incubation of the processed membranes in the presence of human natural anti-Gal IgG resulted in the effective phagocytosis to the tumor membrane by DCs. Eighteen patients aged 38-78 years with stage III primary HCC were randomLy chosen for the study; 9 patients served as controls, and 9 patients were enrolled in the study group.

RESULTS: The evaluation demonstrated that the procedure was safe; no serious side effects or autoimmune diseases were observed. The therapy significantly prolonged the survival of treated patients as compared with the controls (17.1 ± 2.01 mo vs 10.1 ± 4.5 mo, P = 0.00121). After treatment, all patients in the study group had positive delayed hypersensitivity and robust systemic cytotoxicity in response to tumor lysate as measured by interferon-γ-expression in peripheral blood mononuclear cells using enzyme-linked immunosorbent spot assay. They also displayed increased numbers of CD8-, CD45RO- and CD56-positive cells in the peripheral blood and decreased α-fetoprotein level in the serum.

CONCLUSION: This new tumor-specific immunotherapy is safe, effective and has a great potential for the treatment of tumors.

Keywords: Hepatocellular carcinoma, α-Gal epitope, Dendritic cell, Tumor-associated antigen, Dendritic cell-activated cytokine-induced killer cell