Vaccination with dendritic cells pulsed with apoptotic cells elicits effective antitumor immunity in murine hepatoma models.
Dendritic cell (DC)-based vaccine is a developing strategy to treat cancer including hepatoma. We evaluated the antitumor efficacy of vaccination with DCs pulsed with apoptotic cells, as compared to vaccination with DCs pulsed with cell lysates, in murine hepatoma models. Murine hepatoma cells, Hepa1-6, MH134 and BNL1ME.A.7R.1, and their syngeneic mice, C57BL/6, C3H/HeN and BALB/c, respectively, were used in the study. Protective and therapeutic antitumor effects of vaccination with bone marrow-derived DCs pulsed with irradiation or sulindac-induced apoptotic cells or cell lysates were analyzed. Immature DCs efficiently phagocytosed apoptotic cells and increased expression of CD86, a cell surface maturation marker. Vaccination with apoptotic cell-pulsed, but not cell lysate-pulsed, DCs promoted significant protective immunity against parental hepatoma in vivo. Spleen cells from mice vaccinated with apoptotic cell-pulsed DCs showed higher cytolytic activity and contained higher number of IFN-gamma producing cells against parental hepatoma cells than those from mice vaccinated with cell lysate-pulsed DCs in vitro. Polyriboinosinic polyribocytidylic acid [poly (I:C)], double strand RNA, further enhanced CD86 expression and the therapeutic efficacy of vaccination with DCs pulsed with apoptotic cells for pre-established hepatoma. These results suggest that vaccination with DCs pulsed with apoptotic cells and treated with poly (I:C) appears to be a promising approach as a new therapeutic means for hepatoma.
Hayashi
Toshinobu
T
Division of Clinical Pharmaceutics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, Japan.
Nakao
Kazuhiko
K
Nagayama
Yuji
Y
Saitoh
Ohki
O
Ichikawa
Tatsuki
T
Ishikawa
Hiroki
H
Hamasaki
Keisuke
K
Eguchi
Katsumi
K
Ishii
Nobuko
N
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D017209:Apoptosis; D051940:B7-2 Antigen; D019496:Cancer Vaccines / Q000276:immunology*; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000473:pathology / Q000662:veterinary; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D006801:Humans; D007109:Immunity / Q000187:drug effects; D007369:Interferon Inducers / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000276:immunology* / Q000473:pathology / Q000662:veterinary; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011070:Poly I-C / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D051940:B7-2 Antigen; C497964:CD86 protein, human; D019496:Cancer Vaccines; C497965:Cd86 protein, mouse; D007369:Interferon Inducers; D008562:Membrane Glycoproteins; D011070:Poly I-C