An effective cancer vaccine modality: lentiviral modification of dendritic cells expressing multiple cancer-specific antigens.
Viral modification of dendritic cells (DCs) may deliver a "danger signal" critical to the hypo-reactive DCs in cancer patients. Using three highly differentially expressed hepatoma tumor-associated antigens (TAAs): stem cell antigen-2 (Sca-2), glycoprotein 38 (GP38) and cellular retinoic acid binding protein 1 (RABP1), we explored the therapeutic potential of the DCs modified with lentiviral vectors (LVs). Preventive and therapeutic injection of the LV-TAA-DC vaccine into tumor-bearing mice elicited a strong anti-tumor response and extended survival, which was associated with tumor-specific interferon-gamma and cytotoxic T cell responses. In vivo elimination of the LV-TAA-DCs by a co-expressed thymidine kinase suicide gene abrogated the therapeutic effect. The modification of DCs with LVs encoding multiple TAAs offers a great opportunity in cancer immunotherapy.
Wang
Bei
B
Department of Molecular Genetics and Microbiology Powell Gene Therapy Center and McKnight Brain Institute, University of Florida, College of Medicine, Gainesville, FL 32610-0266, USA.
He
Jin
J
Liu
Chen
C
Chang
Lung-Ji
LJ
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D022761:Gene Transfer, Horizontal; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000096:biosynthesis; D016086:Lentivirus / Q000235:genetics*; D008114:Liver Neoplasms, Experimental / Q000276:immunology / Q000628:therapy; D051379:Mice; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D007371:Interferon-gamma