title: Poly-functional and long-lasting anticancer immune response elicited by a safe attenuatedPseudomonas aeruginosavector for antigens delivery.
abstract: Live-attenuated bacterial vectors for antigens delivery have aroused growing interest in the field of cancer immunotherapy. Their potency to stimulate innate immunity and to promote intracellular antigen delivery into antigen-presenting cells could be exploited to elicit a strong and specific cellular immune response against tumor cells. We previously described genetically-modified and attenuatedPseudomonas aeruginosavectors able to deliverin vivoprotein antigens into antigen-presenting cells, through Type 3 secretion system of the bacteria. Using this approach, we managed to protect immunized mice against aggressive B16 melanoma development in both a prophylactic and therapeutic setting. In this study, we further investigated the antigen-specific CD8+T cell response, in terms of phenotypic and functional aspects, obtained after immunizations with a killed but metabolically activeP. aeruginosaattenuated vector. We demonstrated thatP. aeruginosavaccine induces a highly functional pool of antigen-specific CD8+ T cell able to infiltrate the tumor. Furthermore, multiple immunizations allowed the development of a long-lasting immune response, represented by a pool of predominantly effector memory cells which protected mice against late tumor challenge. Overall, killed but metabolically activeP. aeruginosavector is a safe and promising approach for active and specific antitumor immunotherapy.
authors.affiliation: Laboratoire TIMC-TheREx UMR 5525 CNRS-Université Grenoble Alpes, La Tronche, France; APCure SAS, Lyon, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Chauchet
authors.affiliation: APCure SAS , Lyon, France.
authors.forename: Dalil
authors.initials: D
authors.lastname: Hannani
authors.affiliation: CIRI, Centre International de Recherche en Infectiologie, INSERM , Lyon, France.
authors.forename: Sophia
authors.initials: S
authors.lastname: Djebali
authors.affiliation: Laboratoire TIMC-TheREx UMR 5525 CNRS-Université Grenoble Alpes, La Tronche, France; Établissement Français du Sang, La Tronche, France.
authors.forename: David
authors.initials: D
authors.lastname: Laurin
authors.affiliation: Laboratoire TIMC-TheREx UMR 5525 CNRS-Université Grenoble Alpes, La Tronche, France; Département d'Hématologie Oncologie Génétique et Immunologie, Institut de Biologie et Pathologie, C.H.U. de Grenoble,Grenoble, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Polack
authors.affiliation: CIRI, Centre International de Recherche en Infectiologie, INSERM , Lyon, France.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Marvel
authors.affiliation: APCure SAS , Lyon, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Buffat
authors.affiliation: Laboratoire TIMC-TheREx UMR 5525 CNRS-Université Grenoble Alpes, La Tronche, France; Département de Biochimie Toxicologie Pharmacologie, UM Biochimie des Enzymes et des Protéines, Institut de Biologie et Pathologie, C.H.U. de Grenoble, Grenoble, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Toussaint
authors.affiliation: Laboratoire TIMC-TheREx UMR 5525 CNRS-Université Grenoble Alpes, La Tronche, France; Département de Biochimie Toxicologie Pharmacologie, UM Biochimie des Enzymes et des Protéines, Institut de Biologie et Pathologie, C.H.U. de Grenoble, Grenoble, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Le Gouëllec