Activation of cytotoxic T lymphocytes against CML28-bearing tumors by dendritic cells transduced with a recombinant adeno-associated virus encoding the CML28 gene.
Induction of anti-tumor immune responses by dendritic cells (DCs) transduced with a recombinant adeno-associated virus type 2 (rAAV2) encoding tumor antigens is considered a promising approach for cancer vaccine development. CML28, a novel antigen with the properties of cancer/ testis (CT) antigens, is an attractive target for antigen-specific immunotherapy. Here we investigated the feasibility of inducing CML28-specific cytotoxic T lymphocyte (CTL) responses using DCs transduced with the rAAV2 vectors containing the CML28 gene (rAAV/CML28). Using an adenovirus-free packaging system, rAAV/CML28 was generated. The transduction efficiency of rAAV/CML28 in DCs increased in a multiplicity of infection (MOI)-dependent manner. The rAAV/CML28 transduction did not impair DC maturation, but even enhanced the CD80 expression. The rAAV/CML28-transduced DCs induced CML28-specific CTLs which exhibited a MHC class I-mediated antigen-specific lytic activity against CML28-bearing tumor cell lines (HepG2 and MCF-7) as well as the primary leukemia blasts. These findings suggest that rAAV/CML28-transduced DCs vaccine may serve as a feasible approach for the treatment of CML28-associated cancers.
D000256:Adenoviridae / Q000235:genetics*; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D000954:Antigens, Surface / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005095:Exoribonucleases / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D063326:Exosome Multienzyme Ribonuclease Complex; D005240:Feasibility Studies; D005805:Genes, MHC Class I; D006801:Humans; D008213:Lymphocyte Activation; D012333:RNA, Messenger / Q000096:biosynthesis; D016601:RNA-Binding Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D018122:B7-1 Antigen; C467564:EXOSC5 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D005095:Exoribonucleases; D063326:Exosome Multienzyme Ribonuclease Complex