Hepatocellular carcinoma-specific immunotherapy with synthesized alpha 1,3-galactosyl epitope-pulsed dendritic cells and cytokine-induced killer cells

摘要

AIM: To evaluate the safety and clinical efficacy of a new immunotherapy using both alpha-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 alpha 1,3-galactosyl-transferase (alpha 1,3GT) to synthesize alpha-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. 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-gamma-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 alpha-fetoprotein level in the serum. CONCLUSION: This new tumor-specific immunotherapy is safe, effective and has a great potential for the treatment of tumors. (C) 2011 Baishideng. All rights reserved.