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

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.

• Authors: Ying Qiu, Ming-Bao Xu, Mark M Yun, Yi-Zhong Wang, Rui-Ming Zhang, Xing-Kai Meng, Xiao-Hui Ou-Yang, Sheng Yun
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 17 Issue 48 Pg. 5260-6 (Dec 28 2011) ISSN: 2219-2840 [Electronic] United States
• PMID: 22219594 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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