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.
Kao
John Y
JY
Division of Gastroenterology, Department of Internal Medicine, University of Michigan Health System, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0650, USA.
Zhang
Min
M
Chen
Chuan-Min
CM
Chen
Jian-Jun
JJ
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