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


CONCLUSIONS
This new tumor-specific immunotherapy is safe, effective and has a great potential for the treatment of tumors.
The First Teaching Hospital, Inner Mongolia Medical College, Huhhot 010050, Inner Mongolia Autonomous Region, China.
Ying
Y
Qiu
Ming-Bao
MB
Xu
Mark M
MM
Yun
Yi-Zhong
YZ
Wang
Rui-Ming
RM
Zhang
Xing-Kai
XK
Meng
Xiao-Hui
XH
Ou-Yang
Sheng
S
Yun
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D055612:Cytokine-Induced Killer Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D005260:Female; D005700:Galactosyltransferases / Q000235:genetics / Q000378:metabolism; D006023:Glycoproteins / Q000737:chemistry / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged
D000951:Antigens, Neoplasm; D000939:Epitopes; D006023:Glycoproteins; D005700:Galactosyltransferases; C047006:N-acetyllactosaminide alpha-1,3-galactosyltransferase