Superior efficacy of dendritic cell-tumor fusion vaccine compared with tumor lysate-pulsed dendritic cell vaccine in colon cancer.
Dendritic cell (DC)-based tumor vaccine is a promising therapy for malignancies. Recent studies showed greater potency with DC/tumor fusion vaccines against acute myeloid leukemia and melanoma compared with lysate-pulsed DC vaccines. We compared these two vaccine strategies against murine colon cancer and investigated whether DC/tumor fusion cells continue to produce tumor antigens following fusion as a possible explanation for their increased potency. Using a mouse colon cancer model, CT26, we first showed that the DC/CT26 fusion vaccine is more effective in preventing tumor implantation than CT26 lysate-pulsed DC vaccine. Next, CT26 made to constitutively produce bioactive TGF-beta, a surrogate of tumor-derived products, was fused to DCs and found to produce bioactive TGF-beta 72 h after fusion. Our results suggest the DC/tumor fusion vaccine is more potent against colon cancer than the lysate-pulsed DC vaccine. These fusion cells have the distinct advantage of prolonged interaction with tumor antigens in vivo.
Division of Gastroenterology, Department of Internal Medicine, University of Michigan Health System, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0650, USA.
John Y
JY
Kao
Min
M
Zhang
Chuan-Min
CM
Chen
Jian-Jun
JJ
Chen
D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D015415:Biomarkers; D019496:Cancer Vaccines / Q000276:immunology*; D002454:Cell Differentiation; D002457:Cell Extracts / Q000276:immunology*; D002459:Cell Fusion; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation; D007167:Immunotherapy; D051379:Mice; D008807:Mice, Inbred BALB C; D015996:Survival Rate; D016212:Transforming Growth Factor beta / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D000951:Antigens, Neoplasm; D015415:Biomarkers; D019496:Cancer Vaccines; D002457:Cell Extracts; D016212:Transforming Growth Factor beta