Poly-functional and long-lasting anticancer immune response elicited by a safe attenuated Pseudomonas aeruginosa vector for antigens delivery

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 cellul...

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Autores principales: Chauchet, Xavier, Hannani, Dalil, Djebali, Sophia, Laurin, David, Polack, Benoit, Marvel, Jacqueline, Buffat, Laurent, Toussaint, Bertrand, Le Gouëllec, Audrey
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5155632/
https://www.ncbi.nlm.nih.gov/pubmed/28035332
http://dx.doi.org/10.1038/mto.2016.33
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author Chauchet, Xavier
Hannani, Dalil
Djebali, Sophia
Laurin, David
Polack, Benoit
Marvel, Jacqueline
Buffat, Laurent
Toussaint, Bertrand
Le Gouëllec, Audrey
author_facet Chauchet, Xavier
Hannani, Dalil
Djebali, Sophia
Laurin, David
Polack, Benoit
Marvel, Jacqueline
Buffat, Laurent
Toussaint, Bertrand
Le Gouëllec, Audrey
author_sort Chauchet, Xavier
collection PubMed
description 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 attenuated Pseudomonas aeruginosa vectors able to deliver in vivo protein 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 active P. aeruginosa attenuated vector. We demonstrated that P. aeruginosa vaccine 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 active P. aeruginosa vector is a safe and promising approach for active and specific antitumor immunotherapy.
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spelling pubmed-51556322016-12-29 Poly-functional and long-lasting anticancer immune response elicited by a safe attenuated Pseudomonas aeruginosa vector for antigens delivery Chauchet, Xavier Hannani, Dalil Djebali, Sophia Laurin, David Polack, Benoit Marvel, Jacqueline Buffat, Laurent Toussaint, Bertrand Le Gouëllec, Audrey Mol Ther Oncolytics Article 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 attenuated Pseudomonas aeruginosa vectors able to deliver in vivo protein 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 active P. aeruginosa attenuated vector. We demonstrated that P. aeruginosa vaccine 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 active P. aeruginosa vector is a safe and promising approach for active and specific antitumor immunotherapy. Nature Publishing Group 2016-12-14 /pmc/articles/PMC5155632/ /pubmed/28035332 http://dx.doi.org/10.1038/mto.2016.33 Text en Copyright © 2016 Official journal of the American Society of Gene & Cell Therapy http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/
spellingShingle Article
Chauchet, Xavier
Hannani, Dalil
Djebali, Sophia
Laurin, David
Polack, Benoit
Marvel, Jacqueline
Buffat, Laurent
Toussaint, Bertrand
Le Gouëllec, Audrey
Poly-functional and long-lasting anticancer immune response elicited by a safe attenuated Pseudomonas aeruginosa vector for antigens delivery
title Poly-functional and long-lasting anticancer immune response elicited by a safe attenuated Pseudomonas aeruginosa vector for antigens delivery
title_full Poly-functional and long-lasting anticancer immune response elicited by a safe attenuated Pseudomonas aeruginosa vector for antigens delivery
title_fullStr Poly-functional and long-lasting anticancer immune response elicited by a safe attenuated Pseudomonas aeruginosa vector for antigens delivery
title_full_unstemmed Poly-functional and long-lasting anticancer immune response elicited by a safe attenuated Pseudomonas aeruginosa vector for antigens delivery
title_short Poly-functional and long-lasting anticancer immune response elicited by a safe attenuated Pseudomonas aeruginosa vector for antigens delivery
title_sort poly-functional and long-lasting anticancer immune response elicited by a safe attenuated pseudomonas aeruginosa vector for antigens delivery
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5155632/
https://www.ncbi.nlm.nih.gov/pubmed/28035332
http://dx.doi.org/10.1038/mto.2016.33
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