title: Dendritic cell-specific delivery of Flt3L by coronavirus vectors secures induction of therapeutic antitumor immunity.
abstract: Efficacy of antitumor vaccination depends to a large extent on antigen targeting to dendritic cells (DCs). Here, we assessed antitumor immunity induced by attenuated coronavirus vectors which exclusively target DCs in vivo and express either lymphocyte- or DC-activating cytokines in combination with a GFP-tagged model antigen. Tracking of in vivo transduced DCs revealed that vectors encoding for Fms-like tyrosine kinase 3 ligand (Flt3L) exhibited a higher capacity to induce DC maturation compared to vectors delivering IL-2 or IL-15. Moreover, Flt3L vectors more efficiently induced tumor-specific CD8(+) T cells, expanded the epitope repertoire, and provided both prophylactic and therapeutic tumor immunity. In contrast, IL-2- or IL-15-encoding vectors showed a substantially lower efficacy in CD8(+) T cell priming and failed to protect the host once tumors had been established. Thus, specific in vivo targeting of DCs with coronavirus vectors in conjunction with appropriate conditioning of the microenvironment through Flt3L represents an efficient strategy for the generation of therapeutic antitumor immunity.
authors: Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors: Christian
authors: C
authors: Perez-Shibayama
authors: Cristina
authors: C
authors: Gil-Cruz
authors: Monika
authors: M
authors: Nussbacher
authors: Eva
authors: E
authors: Allgäuer
authors: Luisa
authors: L
authors: Cervantes-Barragan
authors: Roland
authors: R
authors: Züst
authors: Burkhard
authors: B
authors: Ludewig
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D017934:Coronavirus / Q000235:genetics*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D005822:Genetic Vectors / Q000235:genetics*; D007167:Immunotherapy / Q000379:methods*; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics* / Q000276:immunology; D051379:Mice; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*
chemical_list: D019496:Cancer Vaccines; D019409:Interleukin-15; D007376:Interleukin-2; D008565:Membrane Proteins; C084881:flt3 ligand protein