Development of anti-tumor immunotherapy mediated by type III secretion system-based live attenuated bacterial vectors
type: Dataset
contact point: Organization
  fn: CCSD
keyword: anti-tumor-immunotherapy
keyword: vecteur-vaccinal-bacterien
keyword: le-systeme-de-secretion-de-type-iii-sstt
keyword: theses
keyword: limmunotherapie-antitumorale
keyword: sdvmheplife-sciences-q-biohuman-health-and-pathology
keyword: the-type-iii-secretion-system
keyword: infoeu-reposemanticsdoctoralthesis
keyword: bacterial-vaccine-vector
landing page: https://theses.hal.science/tel-00767285
description: Due to the endowed effective ability to deliver antigen to cytoplasm of APCs in vivo, T3SS based attenuated bacterial vectors attracted more and more attention for their potential interest in cancer vaccine development. Pseudomonas aeruginosa est un pathogène opportuniste responsable d'infections graves chez les personnes immunodéprimées, les grands brûlés et les patients atteints de la mucoviscidose. Cette pathogénicité repose sur de nombreux facteurs de virulence dont le système de sécrétion de type III (SSTT). In our previous work, the potential of attenuated P. aeruginosa strains as the carriers for anti-tumor vaccination purpose has been reported. In this work, we would like to strengthen P. aeruginosa T3SS based vaccine vectors and direct the development of these bacterial vectors toward clinical applications. First, the performance of these bacterial vectors has been improved in different murine cancer models by: 1) adding one CD4+ Th epitope to vectors; 2) applying bi-antigen expression pattern to vectors; 3) constructing potential humoral response inducing vectors. Second, the therapeutic performance of bacterial vector has been optimized by modulating injection frequency and interval and then be confirmed in murine tumor models. Third, one clinically applicable candidate has been generated by adapting one totally avirulent P. aeruginosa mutant (CHA-OAL) in a chemically defined medium and the poor infectivity of this new strain has been overcome by vaccinations at multiple loci. Fourth, the potential of bacterial vector for human immunotherapy has been further evaluated in one first level humanized mice (HHD) model. Finally, we observed that the pre-existing anti-vector immunity didn't impair the vaccination efficiency of bacteria vector. Taken together, our results highlight the potentials of our live attenuated P. aeruginosa vectors for applications in relevant clinical trials.
identifier: NNT: 2012GRENS010
issued: 2026-05-30T03:26:18.285623
language: fr
modified: 2026-05-30T03:26:18.285631

Development of anti-tumor immunotherapy mediated by type III secretion system-based live attenuated bacterial vectors
type: Distribution
access URL: https://theses.hal.science/tel-00767285
format: HTML
issued: 2026-05-30T03:26:18.432756
modified: 2026-05-30T03:26:18.252366

test_moissonnage_selune
type: Agent