title: Optimization of antitumor immunotherapy mediated by type III secretion system-based live attenuated bacterial vectors.
abstract: Recently, due to their effective ability to deliver antigen to antigen-presenting cells in vivo, type III secretion system-based attenuated bacterial vectors have increasingly attracted attention for their potential interest in cancer vaccine development. We have previously developed live attenuated Pseudomonas aeruginosa type III secretion system-based vectors to deliver in vivo tumor antigens. In this work, we improved the performance of these bacterial vectors through several approaches in different murine cancer models involving non-self-antigens or self-antigens. First, by modulating injection frequency and interval, bacterial vaccination-activated immune response could be enhanced and the in vivo therapeutic efficacy of bacterial vaccines could be improved. The optimized vaccination scheme induced long-lasting CD8+ T cells' response. Second, a dual antigen delivery pattern was successfully applied in our bacterial vectors. Compared with a single antigen delivery vector, biantigen delivery vectors demonstrated several advantages including better tumor rejection efficiency, simplicity of use, and safety. Third, 1 more attenuated mutant-CHA-OAL strain that is totally avirulent in mice was further adapted to grow in a chemically defined medium to comply with current good manufacturing processes. The poor infectivity of this new strain could be overcome by vaccinations at multiple loci, yielding an efficiently improved vaccination performance. Taken together, our results highlight the potential of our live attenuated P. aeruginosa vectors for applications in relevant clinical trials.
authors.affiliation: TheREx, TIMC-IMAG Laboratory, UMR 5525 CNRS, Université Joseph Fourier, Grenoble, France.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Audrey Le
authors.initials: AL
authors.lastname: Gouëllec
authors.forename: Hichem
authors.initials: H
authors.lastname: Chaker
authors.forename: Hoda
authors.initials: H
authors.lastname: Asrih
authors.forename: Benoit
authors.initials: B
authors.lastname: Polack
authors.forename: Bertrand
authors.initials: B
authors.lastname: Toussaint
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D001324:Autoantigens / Q000235:genetics / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D002460:Cell Line; D005260:Female; D023061:Gene Order; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology* / Q000401:mortality / Q000628:therapy*; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000276:immunology; D016896:Treatment Outcome; D014613:Vaccines, Attenuated
chemical_list: D000951:Antigens, Neoplasm; D001324:Autoantigens; D019496:Cancer Vaccines; D014613:Vaccines, Attenuated