Hepatocellular carcinoma-specific immunotherapy with synthesized α1,3- galactosyl epitope-pulsed dendritic cells and cytokine-induced killer cells

World J Gastroenterol. 2011 Dec 28;17(48):5260-6. doi: 10.3748/wjg.v17.i48.5260.

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

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, Neoplasm / chemistry
  • Antigens, Neoplasm / immunology
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / immunology
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / therapy*
  • Cytokine-Induced Killer Cells / cytology
  • Cytokine-Induced Killer Cells / drug effects*
  • Cytokine-Induced Killer Cells / immunology*
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology*
  • Epitopes / immunology*
  • Female
  • Galactosyltransferases / genetics
  • Galactosyltransferases / metabolism
  • Glycoproteins / chemistry
  • Glycoproteins / immunology
  • Humans
  • Immunotherapy / methods*
  • Kaplan-Meier Estimate
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / immunology
  • Liver Neoplasms / pathology
  • Liver Neoplasms / therapy*
  • Male
  • Middle Aged

Substances

  • Antigens, Neoplasm
  • Epitopes
  • Glycoproteins
  • Galactosyltransferases
  • N-acetyllactosaminide alpha-1,3-galactosyltransferase