title: Lentivirally engineered dendritic cells activate AFP-specific T cells which inhibit hepatocellular carcinoma growth in vitro and in vivo.
abstract: α-fetoprotein (AFP), a tumor-associated antigen for hepatocellular carcinoma (HCC), is an established biomarker for HCC. In this study, we created a lentivirus expressing the AFP antigen and investigated the anti-tumor activity of AFP-specific CD8+ T cells, with and without CD4+ T cells, which were activated by either AFP peptide-pulsed or Lenti-AFP-engineered Dendritic cells (DCs) in vitro and in vivo. AFP-specific T cells could efficiently kill HepG2 HCC cells, and produced IL-2, IFN-γ, TNF-α, perforin and granzyme B, with minimal production of IL-10 (a negative regulator of T cell activation). Both strategies activated AFP-specific T cells, but the lentiviral strategy was superior by several measures. Data also support an impact of CD4+ T cells in supporting anti-tumor activity. In vivo studies in a xenograft HCC tumor model also showed that AFP-specific T cells could markedly suppress HCC tumor formation and morbidity in tumor-bearing nude mice, as well as regulate serum levels of related cytokines and anti-tumor molecules. In parallel with human in vitro T cell cultures, the in vivo model demonstrated superior anti-tumor effects and Th1-skewing with Lenti-AFP-DCs. This study supports the superiority of a full-length antigen lentivirus-based DCs vaccine strategy over peptides, and provides new insight into the design of DCs-based vaccines.
authors.affiliation: Shanghai 10th People's Hospital Affiliated to Tongji University, Shanghai 200072, PR China. yliu6633@yahoo.com.cn
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Lisa H
authors.initials: LH
authors.lastname: Butterfield
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Fu
authors.forename: Zhenshun
authors.initials: Z
authors.lastname: Song
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhang
authors.forename: Chongde
authors.initials: C
authors.lastname: Lu
authors.forename: Guanghui
authors.initials: G
authors.lastname: Ding
authors.forename: Mengchao
authors.initials: M
authors.lastname: Wu
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000503:physiopathology; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D000939:Epitopes / Q000276:immunology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics*; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D008113:Liver Neoplasms / Q000276:immunology* / Q000503:physiopathology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008819:Mice, Nude; D010455:Peptides / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D000509:alpha-Fetoproteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
chemical_list: D016207:Cytokines; D000939:Epitopes; D010455:Peptides; D000509:alpha-Fetoproteins