In vitro induction of carcinoembryonic antigen (CEA)-specific cytotoxic T lymphocytes by dendritic cells transduced with recombinant adenoviruses

Abstract

Carcinoembryonic antigen (CEA), which is expressed in several cancer types, is a potential target for specific immunotherapy. In this study, the feasibility of using dendrite cells (DCs) for tumor immunotherapy after transduction with a recombinant adenovirus containing CEA gene (AdVCEA) was investigated. The recombinant AdV provided a highly efficient reproducible gene transfer into monocyte-derived DCs and its efficiency was increased in a multiplicity of infection (MOI)-dependent manner. As consequence of AdVCEA infection, the level of surface CEA on DCs was slightly increased and the dose (MOI) of AdVCEA had no effect on the surface CEA expression. However, the intracellular CEA expression was impressively increased in an MOI-dependent manner. Moreover, the AdVCEA infection had no appreciable effect on apoptosis of DCs compared with that of mock-infected and actinomycin D (AcD)-treated DCs. The AdVCEA-infected DCs-induced CEA-specific proliferative responses and it was higher than that of peptide-loaded DCs. The T-cell lines, primed by the recombinant AdVCEA-infected DCs in vitro, not only recognized CEA peptide-loaded target cells but also CEA-expressing tumor cell lines in a human leukocyte antigen (HLA) class I-restricted manner. Cytotoxic activity toward target cells was found to be mediated primarily by CD8(+) T-cells, although both CD8(+) cells and CD4(+) cells were able to lyse CEA peptide-loaded target cells. These preliminary results suggest that DCs, transduced with AdV encoding CEA, may be used for the development of adoptive cellular immunotherapy and DC-based cancer vaccine for the treatment of CEA-expressing tumors.