Anti-tumor immunotherapy via antigen delivery from a live attenuated genetically engineered Pseudomonas aeruginosa type III secretion system-based vector.
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.
Epaulard
Olivier
O
Groupe de Recherche et d'Etude du Processus Inflammatoire, Université J. Fourier EA2938, Hopital de Grenable, CHU de Grenoble, BP 217, 38043 Grenoble Cedex 09, France. BPolack@chu-grenoble.fr <BPolack@chu-grenoble.fr>
Toussaint
Bertrand
B
Quenee
Lauriane
L
Derouazi
Madiha
M
Bosco
Nabil
N
Villiers
Christian
C
Le Berre
Rozenn
R
Guery
Benoit
B
Filopon
Didier
D
Crombez
Laurence
L
Marche
Patrice N
PN
Polack
Benoit
B
D000818:Animals; D000941:Antigens / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D005818:Genetic Engineering; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D007167:Immunotherapy; D051379:Mice; D009369:Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000628:therapy; D011550:Pseudomonas aeruginosa / Q000235:genetics*
D000941:Antigens