Anti-tumor immunotherapy via antigen delivery from a live attenuated genetically engineered Pseudomonas aeruginosa type III secretion system-based vector.

Olivier Epaulard 1 Bertrand Toussaint 1 Lauriane Quenee 1 Madiha Derouazi 1 Nabil Bosco 2 Christian Villiers 2 Rozenn Le Berre 3 Benoit Guery 3 Didier Filopon 1 Laurence Crombez 1, 4 Patrice Marche 2 Benoit Polack 1, *
* Auteur correspondant
1 GREPI - Groupe de Recherche et d'Etudes du Processus Inflammatoire
2 Contrôle moléculaire de la réponse immune specifique
3 Biologie et physiologie des états septiques
4 Protein'eXpert SA
Abstract : Immunotherapy requiring an efficient T lymphocyte response is initiated by antigen delivery to antigen-presenting cells. Several studies have assessed the efficiency of various antigen loading procedures, including microbial vectors. Here a live strain of Pseudomonas aeruginosa was engineered to translocate a recombinant antigenic protein into mammalian cells via the type III secretion system, a bacterial device translocating effector proteins into host cells. Optimization of the vector included virulence attenuation and determination of the N-terminal sequence allowing translocation of fused antigens into cells. In vitro delivery of an ovalbumin fragment by the bacterial vector into dendritic cells induced the activation of ovalbumin-specific CD8(+) T lymphocytes. Mice injected with the ovalbumin-delivering vector developed ovalbumin-specific CD8(+) T lymphocytes and were resistant to a subsequent challenge with an ovalbumin-expressing melanoma. Moreover, in a curative assay, injection of the vaccine vector 5 and 12 days after tumor implantation led to a complete cure in five of six animals. These results highlight the utility of type III secretion system-based vectors for anti-tumor immunotherapy.
Keywords : cancer immunotherapy vaccine type III secretion system Pseudomonas aeruginosa dendritic cell
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Article dans une revue
Molecular Therapy, Nature Publishing Group, 2006, 14 (5), pp.656-61. 〈10.1016/j.ymthe.2006.06.011〉
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http://www.hal.inserm.fr/inserm-00144349
Contributeur : Patrice Marche <>
Soumis le : jeudi 3 mai 2007 - 05:40:59
Dernière modification le : lundi 16 juillet 2018 - 15:10:56

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Olivier Epaulard, Bertrand Toussaint, Lauriane Quenee, Madiha Derouazi, Nabil Bosco, et al.. Anti-tumor immunotherapy via antigen delivery from a live attenuated genetically engineered Pseudomonas aeruginosa type III secretion system-based vector.. Molecular Therapy, Nature Publishing Group, 2006, 14 (5), pp.656-61. 〈10.1016/j.ymthe.2006.06.011〉. 〈inserm-00144349〉

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