title: A safe bacterial microsyringe for in vivo antigen delivery and immunotherapy.
abstract: The industrial development of active immunotherapy based on live-attenuated bacterial vectors has matured. We developed a microsyringe for antigen delivery based on the type III secretion system (T3SS) of P. aeruginosa. We applied the "killed but metabolically active" (KBMA) attenuation strategy to make this bacterial vector suitable for human use. We demonstrate that attenuated P. aeruginosa has the potential to deliver antigens to human antigen-presenting cells in vitro via T3SS with considerable attenuated cytotoxicity as compared with the wild-type vector. In a mouse model of cancer, we demonstrate that this KBMA strain, which cannot replicate in its host, efficiently disseminates into lymphoid organs and delivers its heterologous antigen. The attenuated strain effectively induces a cellular immune response to the cancerous cells while lowering the systemic inflammatory response. Hence, a KBMA P. aeruginosa microsyringe is an efficient and safe tool for in vivo antigen delivery.
authors.affiliation: TIMC-TheREx Laboratory (UMR 5525 CNRS-UJF), Faculty of Medecine, Université Joseph Fourier Grenoble I, La Tronche, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Le Gouëllec
authors.forename: Xavier
authors.initials: X
authors.lastname: Chauchet
authors.forename: David
authors.initials: D
authors.lastname: Laurin
authors.forename: Caroline
authors.initials: C
authors.lastname: Aspord
authors.forename: Julien
authors.initials: J
authors.lastname: Verove
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Charlotte
authors.initials: C
authors.lastname: Genestet
authors.forename: Candice
authors.initials: C
authors.lastname: Trocme
authors.forename: Mitra
authors.initials: M
authors.lastname: Ahmadi
authors.forename: Sandrine
authors.initials: S
authors.lastname: Martin
authors.forename: Alexis
authors.initials: A
authors.lastname: Broisat
authors.forename: François
authors.initials: F
authors.lastname: Cretin
authors.forename: Catherine
authors.initials: C
authors.lastname: Ghezzi
authors.forename: Benoit
authors.initials: B
authors.lastname: Polack
authors.forename: Joël
authors.initials: J
authors.lastname: Plumas
authors.forename: Bertrand
authors.initials: B
authors.lastname: Toussaint
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000941:Antigens / Q000276:immunology*; D058947:Bacterial Secretion Systems; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology / Q000633:toxicity; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology / Q000382:microbiology; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D011564:Furocoumarins / Q000494:pharmacology; D006801:Humans; D007111:Immunity, Cellular; D007167:Immunotherapy; D008221:Lymphoid Tissue / Q000276:immunology / Q000382:microbiology; D051379:Mice; D009154:Mutation; D009369:Neoplasms / Q000276:immunology / Q000517:prevention & control / Q000628:therapy; D017319:Photosensitizing Agents / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014613:Vaccines, Attenuated / Q000276:immunology / Q000633:toxicity; D023041:Xenograft Model Antitumor Assays
chemical_list: D000941:Antigens; D058947:Bacterial Secretion Systems; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D011564:Furocoumarins; D017319:Photosensitizing Agents; D014613:Vaccines, Attenuated; C118577:amotosalen